Rheumatology-Rhumatologie

WHAT IS ALREADY KNOWN ON THIS TOPICPatients with rheumatoid arthritis (RA) can be divided into seropositive and seronegative subgroups. The presence of antibodies against post-translationally modified (PTM) proteins such as citrullinated proteins is nowadays used as a diagnostic and prognostic marker in RA. Antibodies directed against carbamylated proteins have more recently been shown to be present in a subset of the seronegative patients and are associated with bone erosions in that group.WHAT THIS STUDY ADDSIn this study, two different anti-PTM antibodies are investigated: anti-advanced glycation end-product modified protein antibodies (anti-AGE) and anti-malondialdehyde-acetaldehyde adduct modified protein antibodies (anti-MAA). These antibodies can be detected in several forms of inflammatory arthritis. Within seronegative RA (negative for rheumatoid factor, anti-citrullinated protein antibodies and anti-carbamylated protein antibodies), 16.9% of patients are positive for anti-MAA and/or anti-AGE antibodies. This subgroup is characterised by an association with HLA-DRB1*03, increased radiographic joint damage and (for anti-MAA) inflammation.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYThe presence of anti-PTM antibodies like anti-AGE and anti-MAA in patients with RA and other patients with inflammatory arthritis previously considered to be seronegative, may not only serve as a prognostic marker, but importantly may contribute to understanding the pathogenesis of these conditions, including a subset of RA.IntroductionIn rheumatoid arthritis (RA) around two-thirds of patients are autoantibody positive for rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and/or anti-carbamylated protein (anti-CarP) antibodies.1 The remaining seronegative subgroup of RA is clinically heterogeneous and thus far no reliable biomarkers are available to identify these patients or predict their disease course.1ACPA and anti-CarP are antibodies that recognise proteins that have undergone post-translational modification (PTM), citrullination of arginine and carbamylation of lysine respectively.2 3 However, many other types of PTMs exist.4 Two examples of PTMs that are found to associate with disease are advanced glycation end-products (AGE) and malondialdehyde-acetaldehyde adducts (MAA). AGEs are a result of oxidative stress and tissue damage5 and are, for example, present in patients with diabetes mellitus type 2.6 Interestingly, in these patients also antibodies directed against this PTM were observed.6 MAA modifications are a result of reactive oxygen species that are formed during inflammation and oxidative stress.7 Both MAA-modified proteins and anti-MAA antibodies are found in patients with RA, as well as in other diseases.7 AGE and MAA are both highly immunogenic PTMs.8 9 Therefore, it is plausible that antibodies against AGE and MAA are also present in patients with arthritis.Seronegative RA is associated with HLA-DRB1*03, suggesting a role for immunopathology driven by, for example, B cell immunity.10 Indeed, within the ACPA-negative patients, the presence of anti-CarP was associated with HLA-DRB1*03.11 12 However, it did not yet explain the full HLA-DRB1*03 association, raising the possibility that other anti-PTM responses may be present in ‘seronegative’ RA that are present in the remainder of the HLA-DRB1*03 positive individuals.13 14 On top of this haplotype association, within these patients with ACPA-negative RA, anti-CarP was found to associate with a more severe radiological progression.3 Patients with seronegative RA are a diverse group of patients that in many ways resemble undifferentiated arthritis. Presence of antibodies, like anti-PTM antibodies, might help to better understand and characterise subgroups that possibly belong to this so-called seronegative RA.We therefore investigated whether anti-AGE and anti-MAA antibodies are present in patients with RA and other forms of arthritis, and whether they could potentially close the so-called serological gap1 in seronegative RA.MethodsPatientsOne thousand one hundred eighty-six patients with arthritis of at least one joint and a symptom duration of less than 2 years were included in the Leiden Early Arthritis Clinic (EAC) cohort.15 Data were collected at baseline and follow-up (4, 12 months and yearly thereafter). Patients were being followed as long as the patient remained being seen clinically by the rheumatologist. RA was classified based on the 1987 American College of Rheumatology criteria (n=648).16 Definitive diagnoses other than RA (n=538) were made by the treating physician after 1 year of follow-up and were predominantly psoriatic arthritis (PsA) (n=100), inflammatory osteoarthritis (n=95) and gout (n=93) besides other more rare forms of arthritis. For this manuscript, the following diagnoses were termed autoimmune (AI): RA, PsA, spondyloarthritis, sarcoidosis, systemic lupus erythematosus (SLE) and paraneoplastic arthritis. The diagnoses termed as non-autoimmune (non-AI) were: gout, pseudogout and septic arthritis. Clinical and demographic patient characteristics were collected as described previously.17Genotyping, radiological progression and remissionFrom all patients, HLA genotypes were established as described previously.18 The alleles that were marked as shared epitope-encoding HLA (HLA-SE) positive were: HLA-DRB1*01:01, 01:02, 04:01, 04:04, 04:05, 04:08, 10:01 and 14:02. For the radiological progression analyses, 2853 X-ray sets of the hands and feet of 635 patients with RA were scored as described previously using the Sharp-van der Heijde score (SHS).19 20 Sustained drug-free remission (SDFR) was defined as the absence of clinical synovitis after discontinuation of disease-modifying antirheumatic drug treatment, that persisted for the entire follow-up, being at least 1 year.21Anti-AGE and anti-MAA measurementsAnti-AGE and anti-MAA antibodies were detected using an in-house ELISA based on modified fetal calf serum (FCS) as described previously.22 Briefly, modified and non-modified FCS were coated to a Nunc Maxisorp ELISA plate (430341, Thermofisher). In between each sequential step, plates were washed three times using phosphate buffered saline (PBS)/0.05%Tween (Sigma, P1379). After blocking (PBS/1%bovine serum albumin) for 6 hours at 4°C plates were incubated overnight at 4°C with 1/100 or 1/1000 diluted serum for anti-AGE and anti-MAA, respectively. Each plate contained a standard of anti-PTM positive serum to calculate arbitrary units. After incubation, IgG levels were detected using Rabbit-anti-Human IgG-HRP (Dako, P0214). Plates were developed by incubating with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)/0.015% H2O2 (A1888 and 7722-84-1, both from Merck) and absorbance at 415 nm was measured using a microplate reader (Bio-Rad iMark). The cut-off for positivity was set as the mean arbitrary units plus two times the SD of 80 healthy controls, excluding values higher than 10× the mean.Statistical analysisIndependent samples t-test and Mann-Whitney U tests were used to analyse the baseline characteristics. The association of HLA-DRB1*03 with autoantibodies was assessed with logistic regression, and stratified for anti-cyclic citrullinated peptide 2 (anti-CCP2) and anti-CarP if relevant. Correlations between anti-PTM antibodies and inflammatory markers were calculated using Spearman’s rank correlation. For the radiological progression analyses, a multivariate normal regression model for longitudinal data was used with SHS as response variable. The model controlled for the age, sex and inclusion year of the patients.19 SDFR development until follow-up was calculated using Kaplan-Meier survival analysis and Cox’s regression. All statistical analysis were performed using SPSS statistics V.25 (IBM).ResultsAnti-AGE and anti-MAA in patients with arthritisBaseline characteristics are described in table 1. Anti-PTM antibody levels were measured in RA and non-RA arthritis patients and compared with healthy controls (figure 1A,B and online supplemental table 1). The non-RA arthritis group was divided into subgroups and separately depicted based as AI arthritis (without RA) including PsA, paraneoplastic arthritis, SLE, sarcoidosis and spondyloarthritis and as non-AI arthritis including septic arthritis, gout and pseudogout.Supplemental material[rmdopen-2023-003480supp001.pdf]View inline View popup Table 1 Baseline characteristics of the rheumatoid arthritis (RA), non-RA, autoimmune no RA and non-autoimmune group<img class="highwire-fragment fragment-image" height="440" src="https://rmdopen.bmj.com/content/rmdopen/9/4/e003480/F1.medium.gif"; width="315" alt="Figure 1">Download figure Open in new tab Download powerpoint Figure 1 Anti-AGE and anti-MAA show higher levels in RA and occur in a subgroup of patients with anti-CarP anti-CCP2 negative RA. IgG antibody levels of anti-AGE (A) and anti-MAA (B) in patients with (n=648) and without (n=538) RA. Early patients with arthritis were separately depicted as groups: AI without RA (including psoriatic arthritis, paraneoplastic arthritis, SLE, sarcoidosis and spondyloarthritis) and non-AI (including septic arthritis, gout, pseudogout). (C) Upset plots of groups of patients with RA (n=499*) positive for anti-PTM combinations; anti-AGE, anti-MAA, anti-CarP, anti-CCP2 and RF. *Data for anti-CarP was missing for 149 patients with RA. AGE, advanced glycation end-product; AI, autoimmune; aU/mL, arbitrary units per mL; CarP, carbamylated protein; CCP2, citrullinated cyclic peptide 2; MAA, malondialdehyde acetaldehyde adduct; RA, rheumatoid arthritis; RF, rheumatoid factor.Compared with healthy controls, anti-AGE and anti-MAA were most prevalent in RA (anti-AGE: 7.5% in HC vs 44.6% in RA and anti-MAA: 3.8% in HC vs 46.1% in RA) but were also present in other types of early arthritis. Within patients without RA, anti-AGE and anti-MAA were present in 32.9% and 30.3%, respectively and in non-RA AI arthritis anti-AGE and anti-MAA were found in 38.5% and 41.5%, respectively. These data indicate that the presence of anti-PTM antibodies is not specific for RA. When analysing combinations of autoantibodies, the largest subgroup of patients with RA (n=99) had all four anti-PTM antibodies (anti-AGE, anti-MAA, anti-CarP, anti-CCP2) as well as RF, after which the second largest group (n=63) was characterised by the combination of RF, anti-CCP2 and anti-CarP (figure 1C).Interestingly, 67 (34.0%) and 57 (28.9%) of patients with seronegative (RF negative, ACPA negative and anti-CarP negative) RA were positive for anti-AGE and anti-MAA, respectively. Moreover, 40 (20.3%) of these patients with seronegative RA were positive for both anti-AGE and anti-MAA. These anti-PTM responses may identify a new subgroup in the patients with otherwise seronegative RA.HLA-DRB1*03 associates with anti-AGE and anti-MAA independently of anti-CarP in patients with anti-CCP2-negative RASince HLA class II alleles are known to associate with autoantibody positivity in RA, we sought to investigate the presence of HLA-SE and its association with anti-AGE and anti-MAA antibodies. Of all patients with RA, 63.3% were HLA-SE+ (table 1). Based on the well-known association between HLA-SE and RA, the HLA-SE alleles were assessed and were significantly more prevalent in all RA subgroups compared with healthy controls. In the anti-AGE-positive group, as compared with patients with anti-AGE-negative RA however, the prevalence of HLA-SE alleles was similar (table 2). The same was true for anti-MAA; therefore, both anti-AGE and anti-MAA antibodies were not associated with HLA-SE.View inline View popup Table 2 Association between anti-AGE and anti-MAA antibodies and HLA-SE and HLA-DRB1*03 presence in RA and HLA-DRB1*03 presence in non-RA patients from the Leiden EAC cohortSince HLA-DRB1*03 is associated with seronegative RA and anti-CarP antibodies in this disease subset, we sought to investigate the association of HLA-DRB1*03 with anti-AGE and anti-MAA. In patients with RA, HLA-DRB1*03 was more prevalent in anti-AGE-positive and anti-MAA-positive patients as compared with healthy controls with OR values of 1.34 (95% CI 1.01 to 1.78, p=0.05) and 1.29 (95% CI 0.96 to 1.73, p=0.09), although this did not achieve statistical significance compared with anti-AGE-negative or anti-MAA-negative patients, respectively (table 2, part I). To investigate whether HLA-DRB1*03 is associated with anti-MAA and anti-AGE in anti-CCP2-negative RA, we focused on this subset and stratified the analysis for anti-CarP. Within the patients with anti-CCP2 negative RA, anti-AGE and anti-MAA antibodies were associated with HLA-DRB1*03 compared with healthy controls (OR: 1.98, 95% CI 1.27 to 3.07, p=0.003, and OR: 2.37, 95% CI 1.50 to 3.74, p<0.001, respectively). Anti-MAA was associated with HLA-DRB1*03 in the anti-CCP2 negative stratum independent of anti-CarP (OR: 1.91, 95% CI 1.11 to 3.30, p=0.02) (table 2, part II). In this stratified analysis, anti-AGE showed the same trend for association but did not reach significance (OR: 1.48, 95% CI 0.86 to 2.52, p=0.16). Since anti-AGE and anti-MAA often co-occur, we next stratified the association analysis for these autoantibodies, to dissect whether the observed association to HLA-DRB1*03 could be attributed to one of them in particular. After stratification for anti-AGE or anti-MAA, only patients with double positive RA showed a significant association with HLA-DRB1*03 compared with healthy controls (online supplemental table 2, part I). Since some controversy exists on the association of HLA-DRB1*03 in patients with anti-CCP2 negative RA, we investigated the association between anti-AGE and anti-MAA with HLA-DRB1*03 within patients with HLA-SE negative RA. In both HLA-SE negative and anti-CCP2 negative stratum, we find similar associations with anti-AGE/-MAA and HLA-DR1*03 (table 2, part III).In non-RA arthritis patients, both anti-AGE and anti-MAA showed a similar association with HLA-DRB1*03 with OR values of 2.34 (95% CI 1.58 to 3.47, p<0.001) and 1.94 (95% CI 1.29 to 2.92, p=0.002) compared with healthy controls (table 2, part I). In a comparison within the non-RA arthritis patients, HLA DRB1*03 remained significantly associated with anti-AGE-positive compared with anti-AGE-negative patients (OR: 2.22, 95% CI 1.28 to 3.84, p=0.01), while the association with anti-MAA did not remain significant. To disentangle the effects of anti-AGE and anti-MAA, analyses were again stratified, after which only the presence of anti-AGE in patients with anti-MAA-negative without RA remained significantly associated with HLA-DRB1*03 (online supplemental table 2, part II).Taken together, these data indicate that anti-AGE and anti-MAA associate with HLA-DRB1*03 in RA and non-RA arthritis patients, and that this association (which cannot be ascribed to anti-AGE or anti-MAA in particular) is mainly present in patients with anti-CCP2 negative RA. Similar associations were observed in patients with HLA-SE negative RA.Inflammation markers associate with anti-MAA positivity in RA and non-RA arthritisNext, we sought to investigate whether anti-PTM antibodies correlate with inflammation markers erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) (table 3). Higher inflammation parameters in anti-AGE- and anti-MAA-positive individuals were observed in RA and non-RA arthritis patients, and in both the autoimmune and non-autoimmune subgroups of patients with arthritis. To investigate whether both anti-MAA and anti-AGE were associated with acute phase reactants in RA independently, anti-AGE and anti-MAA were stratified for each other. After this stratification, anti-AGE was no longer associated with either CRP or ESR whereas the association of anti-MAA with these inflammation markers remained significant (online supplemental table 3). These data indicate that anti-PTM responses, especially anti-MAA, is associated with markers of inflammation in early arthritis in both RA and non-RA arthritis patients.View inline View popup Table 3 Association between anti-AGE and anti-MAA antibin RA and non-RA arthritis patientsodies and ESR and CRP levelsAnti-AGE and anti-MAA associate with radiological progression in patients with anti-CCP2-negative RAWe next analysed if the presence of anti-AGE and anti-MAA is associated with radiological progression in RA. Anti-AGE-positive patients displayed more radiographic damage per year than anti-AGE-negative patients (p<0.001) (figure 2A). Data were then stratified for anti-CCP2, which revealed that this association was mainly present in the anti-CCP2-negative subgroup (figure 2B). When anti-CCP2 negative patients were further stratified for anti-CarP, the association between anti-AGE and radiographic progression remained significant (figure 2C). This indicates that in patients with anti-CCP2 negative RA, anti-AGE is associated with radiological progression independent of anti-CarP, suggesting that this anti-PTM antibody could discriminate a different subgroup. Anti-MAA positivity was also associated with radiological progression (p=0.002) (figure 2D). This effect was also observed in the anti-CCP2-negative stratum (figure 2E), although no longer significant after stratifying for anti-CCP2. The latter could be a consequence of power as the effect size (beta) which decreased only slightly to 1.03/year, p=0.16 (figure 2E).<img width="393" alt="Figure 2" height="440" class="highwire-fragment fragment-image" src="https://rmdopen.bmj.com/content/rmdopen/9/4/e003480/F2.medium.gif">Download figure Open in new tab Download powerpoint Figure 2 Anti-AGE and anti-MAA associate with radiological progression in patients with RA (n=600). (A) Radiological progression in anti-AGE positive and negative RA. (B) Data stratified for CCP2. (C) Data stratified for anti-CarP in anti-CCP2-negative stratum. (D) Radiological progression in anti-MAA positive and negative RA. (E) Data stratified for CCP2. Data presented as estimate (95% CI), p value. AGE, advanced glycation end-product; CarP, carbamylated protein; CCP2, citrullinated cyclic peptide 2; MAA, malondialdehyde acetaldehyde adduct.Presence of anti-MAA or anti-AGE is not associated with SDFR in RANext, we sought to investigate whether anti-AGE and anti-MAA were associated with SDFR over time (online supplemental figure 3). Anti-AGE was not associated with SDFR, HR 0.93 (95% CI 0.66 to 1.30; p=0.66) which did not differ after adjusting for CCP2 status (HR 1.14, 95% CI 0.81 to 1.61, p=0.46). Anti-MAA-positive patients were less likely to achieve SDFR, compared with anti-MAA-negative patients, HR 0.72 (95% CI 0.51 to 1.00, p=0.053). After adjusting for CCP2 status, there was no longer an association between anti-MAA and SDFR, HR 1.05 (95% CI 0.74 to 1.50, p=0.80).DiscussionIn this study, we demonstrated that anti-AGE and anti-MAA are present in patients with RA, and interestingly also in a substantial part of patients with otherwise seronegative RA. This is not specific for RA, as anti-AGE and anti-MAA antibodies were also present in other forms of early arthritis. Both anti-AGE and anti-MAA are associated with HLA-DRB1*03 in RA, and anti-AGE is also associated with HLA-DR1*03in non-RA arthritis patients. Anti-AGE and anti-MAA are associated with a distinct clinical phenotype: anti-AGE associates with radiological progression in RA whereas anti-MAA only showed a trend with radiological progression but associated with increased inflammatory parameters in both RA and non-RA arthritis.Associations with particular HLA class II alleles have been described to occur in many seropositive AI diseases.13 14 More specifically, HLA-DRB1*03, initially reported to be associated with anti-CCP2 negative RA, was later associated with the presence of anti-CarP, although not all HLA-DRB1*03-positive patients were anti-CarP-positive.10 12 In this study, we observed that HLA-DRB1*03 was associated with anti-AGE and anti-MAA in patients with anti-CCP2 negative RA which was independent of anti-CarP, thereby identifying another subgroup of anti-CCP2 negative RA that is associated with HLA-DRB1*03. In addition, anti-AGE associated with HLA-DRB1*03 in non-RA confirming the robustness of this finding. Together, these observations provide additional insight into the association of HLA-DBR1*03 with (rheumatoid) arthritis; although these alleles are not associated with the presence of ACPA, they do appear to predispose to the formation of other autoantibodies (anti-CarP, anti-AGE and anti-MAA) in a process in which HLA class II-associated T-cell-dependent immune responses are likely to be involved.Interestingly, in RA, anti-AGE associated with radiological progression independent of anti-CCP2 and anti-CarP suggesting an additive value of anti-AGE in determining disease evolution as it could define a new subgroup of patients with RA. Strikingly, anti-AGE was not associated with SDFR. In RA and non-RA, a subgroup of patients is characterised by more extensive inflammation and the presence of anti-MAA antibodies, while a subgroup of patients with CCP2-negative RA is characterised by radiological progression and presence of anti-AGE antibodies. Based on these results, distinct subgroups within RA and non-RA can be delineated based on their specific clinical phenotype.The presence of AGE-modified proteins and anti-AGE antibodies has been observed in diabetes and hypertension.6 23 Also, in synovial tissue and sera of patients with RA, AGE-modified proteins have been detected.24–26 In addition, MAA-modified proteins have been observed before in RA tissue7 and it is clear that both modifications can be induced by inflammation and oxidative stress in the inflamed joint.5 7 Our study now adds that in a subset of the patients with RA antibodies against these PTMs are present. Additionally, anti-AGE and anti-MAA have been found to be associated with ESR in previous studies in RA and SLE.22 PTMs and anti-PTMs such as anti-AGE and anti-MAA add to the understanding that the combined presence of the antigen and the antibody could trigger effector mechanisms and contribute to the overall process of arthritis and joint damage, in RA and also in non-RA. It would therefore be interesting to investigate whether next to carbamylated proteins27 also the modifications AGE and MAA are present in cartilage and synovium. Additionally, experimental pathogenicity studies on anti-AGE and anti-MAA specifically should be performed to elucidate on the contribution of these anti-PTM antibodies to pathogenesis.There are some limitations to our study. Data on anti-CarP antibody levels were missing for 149 patients with RA; therefore, analysis using stratification including anti-CarP could only be performed in a subgroup of all patients with RA. However, this group still consists of 499 patients with RA and therefore still appears a good representation of the RA population. Radiological progression was assessed in 635 patients with RA included before 2006. Thereafter, radiographs have not been scored since radiographic damage has become rare/nearly non-existent with current treatment strategies. This effectively enabled us to detect differences in the, earlier, informative part of the cohort. When stratifying radiological progression data, groups became small and therefore could suffer from insufficient power implicating that significance could not always be reached. It is therefore important to verify associations using different and/or bigger cohorts to be able to generalise findings to the whole RA population. Additionally, in order to verify the results obtained in this study, a replication cohort is needed. In such a study, IgA and IgM responses could be included to elaborate on the full anti-PTM antibody responses in patients with (rheumatoid) arthritis.28 29 One of the strengths of this study is that the EAC is a well-defined cohort containing RA and non-RA early arthritis patients with extensive information on the HLA haplotype and radiological progression for patients with RA.15 Second, antibody responses have been investigated on the PTM-modified proteins and their control proteins. All PTMs were created on the same antigen backbone and reactivity against FCS itself was subtracted from the results. This results in reliable measurements that capture truly PTM-specific signals and decreases the chance of false observations.30 Additionally, correlation analyses were performed (data not shown) and data were stratified for the other investigated anti-PTM and to verify that anti-AGE and anti-MAA are solely responsible for the observed result and not cross-reactive.In conclusion, anti-AGE and anti-MAA antibodies are both prevalent in patients with RA, and other inflammatory rheumatic conditions, and although not specific for RA they each correlate with specific parameters. Anti-MAA associates with HLA-DRB1*03 in CCP2-negative (RA) patients independent of anti-CarP and associates with inflammation. Anti-AGE associates with HLA-DRB1*03 in patients with CCP2-negative RA and is associated with a worse radiological progression especially in patients with anti-CCP2-negative and anti-CarP-negative RA. With this study, we have now characterised a seropositive subgroup within the heterogeneous group of patients with RA that have been thus far been considered seronegative.Data availability statementData are available upon reasonable request. Requests can be sent to l.a.trouw@lumc.nl.Ethics statementsPatient consent for publicationNot applicable.Ethics approvalThe Leiden Early Arthritis Clinic (EAC) cohort was approved by the Medical Ethics Committee Leiden The Hague Delft under reference number: B19.008. For the current study, measurement of anti-PTM antibodies in serum from the EAC cohort is approved under reference number B15.003. Participants gave informed consent to participate in the study before taking part.AcknowledgmentsWe thank Marloes Verstappen and Bianca M. Boxma-de Klerk for their assistance regarding the remission analysis on EAC cohort data.References↵Trouw LA, Mahler M. 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Audio Rheum Editor’s Picks Dr. Earl D. Silverman, MD, shares his monthly Editor’s Picks and their relevance in current clinical practice: June 2023 Featured articles:​ Kiltz, et al: Clinimetric Validation of the Assessment of Spondyloarthritis International Society Health Index in Patients With Radiographic Axial Spondyloarthritis in Ixekizumab Trials Alduraibi, et al: Clustering Patients With Gout Based on Comorbidities and Biomarkers: A Cross-Sectional Study Primeau, et al: Responders to Medial Opening Wedge High Tibial Osteotomy for Knee Osteoarthritis Kumthekar, et al: Physical Activity Habits Among Older Adults Living With Rheumatic Disease Wohlfahrt, et al: Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis May 2023 Featured articles:​ Cook, et al: Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines Against COVID-19 Infection Among Patients With Systemic Autoimmune Rheumatic Diseases on Immunomodulatory Medications Chen, et al: Validation of the Antineutrophil Cytoplasmic Antibody Renal Risk Score and Modification of the Score in a Chinese Cohort With a Majority of Myeloperoxidase-Positive Patients Gorzewski, et al: Predicting Disease Activity in Rheumatoid Arthritis With the Fibromyalgia Survey Questionnaire: Does the Severity of Fibromyalgia Symptoms Matter? Oguro, et al: Effect of Communicative and Critical Health Literacy on Trust in Physicians Among Patients With Systemic Lupus Erythematosus (SLE): The TRUMP2-SLE Project Barber, et al: Investigating Associations Between Access to Rheumatology Care, Treatment, Continuous Care, and Healthcare Utilization and Costs Among Older Individuals With Rheumatoid Arthritis April 2023 Featured articles:​ Coates, et al: Sex-Specific Differences in Patients With Psoriatic Arthritis: A Systematic Review Johnson, et al: Evaluating the Threshold Score for Classification of Systemic Lupus Erythematosus Using the EULAR/ACR Criteria Gong, et al: The Association Between Quadriceps Strength and Synovitis in Knee Osteoarthritis: An Exploratory Study From the Osteoarthritis Initiative Jatuworapruk, et al: Prevalence, Risk Factors, and Outcomes of Gout Flare in Patients Hospitalized for PCR-Confirmed COVID-19: A Multicenter Retrospective Cohort Study Bosch, et al: Etanercept Withdrawal and Retreatment in Nonradiographic Axial Spondyloarthritis: Results of RE-EMBARK, an Open-Label Phase IV Trial March 2023 Featured articles:​ Takanashi, et al: Effects of Aging on Rheumatoid Factor and Anticyclic Citrullinated Peptide Antibody Positivity in Patients With Rheumatoid Arthritis Kiltz, et al: Clinically Relevant Deficits in Performance Tests in Patients With Axial Spondyloarthritis Schletzbaum, et al: Age-Stratified 30-day Rehospitalization and Mortality and Predictors of Rehospitalization Among Patients With Systemic Lupus Erythematosus: A Medicare Cohort Study Berard, et al: Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis Schultz, et al: B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab February 2023 Featured articles:​ Macfarlane, et al: Inflammatory Bowel Disease Risk in Patients With Axial Spondyloarthritis Treated With Biologic Agents Determined Using the BSRBR-AS and a MetaAnalysis Gossec, et al: Women With Psoriatic Arthritis Experience Higher Disease Burden Than Men: Findings From a Real-World Survey in the United States and Europe Davis, et al: The Effect of Psychiatric Comorbidity on Healthcare Utilization for Youth With Newly Diagnosed Systemic Lupus Erythematosus Pyo, et al: The Reclassification of Patients With Previously Diagnosed Eosinophilic Granulomatosis With Polyangiitis Based on the 2022 ACR/EULAR Criteria for Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Weng, et al: Adult-Onset Still Disease After ChAdOx1 nCOV-19 Vaccination Mitchell, et al: How to Provide Sexual and Reproductive Health Care to Patients: Focus Groups With Rheumatologists and Rheumatology Advanced Practice Providers January 2023 Featured articles:​ Kodishala, et al: Risk Factors for Dementia in Patients With Incident Rheumatoid Arthritis: A Population-Based Cohort Study Beauvais, et al: Development and Validation of a Self-Administered Questionnaire Measuring Essential Knowledge in Patients With Axial Spondyloarthritis Orbai, et al: Impact of Physician-Defined Flares on Quality of Life and Work Impairment: An International Survey of 2238 Patients With Psoriatic Arthritis Smitherman, et al: Patient-Reported Outcomes Among Transition-Age Young Adults With Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry Stull, et al: Cutaneous Involvement in Systemic Lupus Erythematosus: A Review for the Rheumatologist Masi, et al: Reflections for the 50th Anniversary of The Journal of Rheumatology: The Past, Present, and Future of Rheumatology Santos, et al: A Rare Case of Subcutaneous Sarcoidosis in Patient With Psoriatic Arthritis Garg, et al: Timing and Predictors of Incident Cardiovascular Disease in Systemic Lupus Erythematosus: Risk Occurs Early and Highlights Racial Disparities December 2022 Featured articles:​ Koo, et al: Relationship Between Inflammation and Radiographic Progression in Patients With Ankylosing Spondylitis Attaining a BASDAI of Less Than 4 During Tumor Necrosis Factor Inhibitor Treatment Sun, et al: Development and Initial Validation of a Systemic Lupus Erythematosus–Specific Measure of the Extent of and Reasons for Medication Nonadherence Patterson, et al: Physical Activity Associates With Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis Coleman, et al: Long-Term Follow-up of a Randomized Controlled Trial of Allopurinol Dose Escalation to Achieve Target Serum Urate in People With Gout Smith: Rusty and Wooden Tanomogi, et al: Extravascular Necrotizing Granuloma: A Diagnostic Clue for Eosinophilic Granulomatosis With Polyangiitis Isnardi, et al: Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines November 2022 Featured articles:​ Nelson, et al: Narrative Review of Machine Learning in Rheumatic and Musculoskeletal Diseases for Clinicians and Researchers: Biases, Goals, and Future Directions Hermans, et al: Are All Routine Spondyloarthritis Outpatient Visits Considered Useful by Rheumatologists? An Exploratory Clinical Practice Study Kallas, et al: Trajectory of Damage Accrual in Systemic Lupus Erythematosus Based on Ethnicity and Socioeconomic Factors Nozawa, et al: Early Abnormal Nailfold Capillary Changes Are Predictive of Calcinosis Development in Juvenile Dermatomyositis Chevet, et al: COVID-19 Vaccine Uptake Among Patients With Systemic Lupus Erythematosus in the American Midwest: The Lupus Midwest Network (LUMEN) Remize, et al: Melorheostosis or “Dripping Candle Wax” Bone Disease Bermas: The Unintended Consequence of the Overturn of Roe v Wade: Restrictions on Methotrexate Use October 2022 Featured articles:​ Hazlewood, et al: Canadian Rheumatology Association Living Guidelines for the Pharmacological Management of Rheumatoid Arthritis With Disease-Modifying Antirheumatic Drugs Schneeberger, et al: Simplified Ankylosing Spondylitis Disease Activity Score (SASDAS) Versus ASDAS: A Post Hoc Analysis of a Randomized Controlled Trial Kasiem, et al: A Practical Guide for Assessment of Skin Burden in Patients With Psoriatic Arthritis Tollisen, et al: Personally Generated Quality of Life Outcomes in Adults With Juvenile Idiopathic Arthritis Glintborg, et al: Long-term Behavioral Changes During the COVID-19 Pandemic and Impact of Vaccination in Patients With Inflammatory Rheumatic Diseases September 2022 Featured articles:​ Cagnotto, et al: Male Sex Predicts a Favorable Outcome in Early ACPA-Negative Rheumatoid Arthritis: Data From an Observational Study Hazlewood, et al: Frequency of Symptomatic Adverse Events in Rheumatoid Arthritis: An Exploratory Online Survey John M. Davis III: The Patient Experience of Drug Side Effects in Rheumatoid Arthritis: Intriguing Data From an Exploratory Online Survey Venkatachalam, et al: Taking the Long View: Patients Perceive Benefits and Risks of Treatment as Multidimensional Wallace, et al: The Association of Illness-related Uncertainty With Mental Health in Systemic Autoimmune Rheumatic Diseases August 2022 Featured articles:​ Verweij, et al: Whole-Body Macrophage Positron Emission Tomography Imaging for Disease Activity Assessment in Early Rheumatoid Arthritis Nguyen, et al: Secukinumab in United States Biologic-Naïve Patients With Psoriatic Arthritis: Results From the Randomized, Placebo-Controlled CHOICE Study Le Ralle, et al: Patient Acceptable Symptom State for Burden From Appearance Changes in People With Systemic Sclerosis: A Cross-sectional Survey Baggett, et al: Incidence Rates of Psoriasis in Children With Inflammatory Bowel Disease and Juvenile Arthritis Treated With Tumor Necrosis Factor Inhibitors and Disease-Modifying Antirheumatic Drugs Carluzzo, et al: Patient Empowerment Among Adults With Arthritis: The Case for Emotional Support July 2022 Featured articles:​ Kelty, et al: Mortality Rates in Patients With Ankylosing Spondylitis With and Without Extraarticular Manifestations and Comorbidities: A Retrospective Cohort Study Mease, et al: Baseline Disease Activity Predicts Achievement of cDAPSA Treatment Targets With Apremilast: Phase III Results in DMARD-naïve Patients With Psoriatic Arthritis Kuwana, et al: Tacrolimus in Patients With Interstitial Pneumonia Associated With Polymyositis or Dermatomyositis: Interim Report of Postmarketing Surveillance in Japan Kiadaliri, et al: Gout and Hospital Admission for Ambulatory Care–Sensitive Conditions: Risks and Trajectories McDermott, et al: Demographic, Lifestyle, and Serologic Risk Factors for Rheumatoid Arthritis (RA)–associated Bronchiectasis: Role of RA-related Autoantibodies June 2022 Featured articles:​ Darabian, et al: Using FibroScan to Assess for the Development of Liver Fibrosis in Patients With Arthritis on Methotrexate: A Single-center Experience Maguire, et al: Central Obesity in Axial Spondyloarthritis: The Missing Link to Understanding Worse Outcomes in Women? Miloslavsky, et al: The Challenge of Addressing the Rheumatology Workforce Shortage Maheswaranathan, et al: Association of Health Literacy and Numeracy With Lupus Knowledge and the Creation of the Lupus Knowledge Assessment Test Emad, et al: Why Do Patients With Gout Not Take Allopurinol? May 2022 Featured articles:​ Movahedi, et al: Physician- and Patient-reported Effectiveness Are Similar for Tofacitinib and TNFi in Rheumatoid Arthritis: Data From a Rheumatoid Arthritis Registry El Tal, et al: Consensus Approach to a Treat-to-target Strategy in Juvenile Idiopathic Arthritis Care: Report From the 2020 PR-COIN Consensus Conference Thompson, et al: Modifiable Factors and Incident Gout Across Ethnicity Within a Large Multiethnic Cohort of Older Adults Widdifield, et al: COVID-19 Vaccination Uptake Among Individuals With Immune-mediated Inflammatory Diseases in Ontario, Canada, Between December 2020 and October 2021: A Population-based Analysis Van Praet, et al: Acute Perimyocarditis in a Case of Multisystem Inflammatory Syndrome in Adults Chang, et al: Systemic Lupus Erythematosus Increases the Risk of Gestational Diabetes: Truth or Illusion? McCormick and Choi: Racial Disparities in the Modern Gout Epidemic ​ April 2022 Featured articles:​ Exarchou, et al: Lifestyle Factors and Disease Activity Over Time in Early Axial Spondyloarthritis: The SPondyloArthritis Caught Early (SPACE) Cohort - https://doi.org/10.3899/jrheum.210046 van Vollenhoven, et al: Efficacy and Safety of Ustekinumab in Patients With Active Systemic Lupus Erythematosus: Results of a Phase II Open-label Extension Study - https://doi.org/10.3899/jrheum.210805 Giancane, et al: Anakinra in Patients With Systemic Juvenile Idiopathic Arthritis: Long-term Safety From the Pharmachild Registry - https://doi.org/10.3899/jrheum.210563 Barber, et al: Best Practices for Virtual Care: A Consensus Statement From the Canadian Rheumatology Association - https://doi.org/10.3899/jrheum.211017 Zickuhr and Mandell: Rheumatology Education Needs a Splash of Color - https://doi.org/10.3899/jrheum.211233 Li, et al: Brain Abscess Due to Nocardia in a Patient With Systemic Lupus Erythematosus- https://doi.org/10.3899/jrheum.210971 ​ March 2022 Featured articles:​ te Kampe, et al: Outcomes of Care Among Patients With Gout in Europe: A Cross-sectional Survey - https://doi.org/10.3899/jrheum.210009 Stransky, et al: Exploring Family Planning, Parenting, and Sexual and Reproductive Health Care Experiences of Men With Rheumatic Diseases - https://doi.org/10.3899/jrheum.210785 Beckers, et al: Performance of 3 Composite Measures for Disease Activity in Peripheral Spondyloarthritis - https://doi.org/10.3899/jrheum.210075 Sun, et al: Long-term Risk of Heart Failure and Other Adverse Cardiovascular Outcomes in Granulomatosis With Polyangiitis: A Nationwide Cohort Study - https://doi.org/10.3899/jrheum.210677 Curtis, et al: Characteristics, Comorbidities, and Outcomes of SARS-CoV-2 Infection in Patients With Autoimmune Conditions Treated With Systemic Therapies: A Population-based Study - https://doi.org/10.3899/jrheum.210888 Gunasuntharam: Why Should It Be Different From the Other Side? A Parent and Pediatrician’s Perspective of a Child With Kawasaki Disease - https://doi.org/10.3899/jrheum.211159 Lazarou, et al: Adult-onset Acute Calcific Discitis - https://doi.org/10.3899/jrheum.210838 Khanna: Remission in Gout: Concepts From a Patient Perspective - https://doi.org/10.3899/jrheum.211285 Coates and Tillett: How Should We Measure Peripheral Spondyloarthritis? - https://doi.org/10.3899/jrheum.211043 ​February 2022 Featured articles:​ Rosenbaum, et al: The Interplay Between COVID-19 and Spondyloarthritis or Its Treatment - https://doi.org/10.3899/jrheum.210742 van der Heijde, et al: Radiographic Progression of Structural Joint Damage Over 5 Years of Baricitinib Treatment in Patients With Rheumatoid Arthritis: Results From RA-BEYOND - https://doi.org/10.3899/jrheum.210346 van der Meer, et al: Extraskeletal Manifestations in Axial Spondyloarthritis Are Associated With Worse Clinical Outcomes Despite the Use of Tumor Necrosis Factor Inhibitor Therapy - https://doi.org/10.3899/jrheum.210308 Haddad, et al: The Association of Psoriatic Arthritis With All-cause Mortality and Leading Causes of Death in Psoriatic Arthritis - https://doi.org/10.3899/jrheum.210159 Yazdanyar, et al: Risk of 30-day Readmission After Knee or Hip Replacement in Rheumatoid Arthritis and Osteoarthritis by Non-Medicare and Medicare Payer Status - https://doi.org/10.3899/jrheum.201370 Perez Acosta et al: Cystic Ganglionosis in a 3-year-old Mimicking Juvenile Idiopathic Arthritis - https://doi.org/10.3899/jrheum.210558 Leung: Is Psoriatic Arthritis Associated With Higher Risk of Mortality? - https://doi.org/10.3899/jrheum.210963 January 2022 Featured articles:​ Bermas, et al: COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance - https://doi.org/10.3899/jrheum.210480 Hazlewood, et al: Heterogeneity in Patient Characteristics and Differences in Treatment Across 4 Canadian Rheumatoid Arthritis Cohorts - https://doi.org/10.3899/jrheum.201688 Panopoulos, et al: Anti-interleukin 6 Therapy Effect for Refractory Joint and Skin Involvement in Systemic Sclerosis: A Real-world, Single-center Experience - https://doi.org/10.3899/jrheum.210273 Lieber, et al: Evaluation of a Patient-reported Frailty Tool in Women With Systemic Lupus Erythematosus - https://doi.org/10.3899/jrheum.201466 Philpott, et al: Synovitis Is Associated With Constant Pain in Knee Osteoarthritis: A Cross-sectional Study of OMERACT Knee Ultrasound Scores - https://doi.org/10.3899/jrheum.210285 Fernandes, et al: Tuberculosis Presenting as an Inflammatory Pseudotumor of the Sciatic Nerve in a Rheumatoid Arthritis Patient Taking Etanercept - https://doi.org/10.3899/jrheum.210540 Sammaritano: The Effect of COVID-19 Illness on Pregnant Patients With Rheumatic Disease: Early Reassuring Data - https://doi.org/10.3899/jrheum.211050 December 2021 Featured articles:​ Kremer, et al: The Clinical Disease Activity Index and the Routine Assessment of Patient Index Data 3 for Achievement of Treatment Strategies - https://doi.org/10.3899/jrheum.200692 Müskens, et al: Does Etanercept Biosimilar Prescription in a Rheumatology Center Bend the Medication Cost Curve? - https://doi.org/10.3899/jrheum.200565 Gladman, et al: Oligoarticular vs Polyarticular Psoriatic Arthritis: A Longitudinal Study Showing Similar Characteristics - https://doi.org/10.3899/jrheum.210434 Showalter, et al: Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis - https://doi.org/10.3899/jrheum.210533 Holyer, et al: What Represents Treatment Efficacy in Long-term Studies of Gout Flare Prevention? An Interview Study of People With Gout - https://doi.org/10.3899/jrheum.210476 Tam et al: My Hips Hurt: An Unusual Presentation of Bilateral Groin Pain in an Adolescent Boy - https://doi.org/10.3899/jrheum.210362 Ferreira, et al: Definition of Treatment Targets in Rheumatoid Arthritis: Is It Time for Reappraisal? - https://doi.org/10.3899/jrheum.210050 Jacobs, et al: Unravelling the Cost of Biological Strategies in Rheumatoid Arthritis: A Kaleidoscope of Methodologies, Interpretations, and Interests - https://doi.org/10.3899/jrheum.201510 ​ November 2021 Featured articles:​ Colantonio, et al: Higher Serum Urate Levels Are Associated With an Increased Risk for Sudden Cardiac Death - https://doi.org/10.3899/jrheum.210139 Ochi, et al: Similarity of Response to Biologics Between Elderly-onset Rheumatoid Arthritis (EORA) and Non-EORA Elderly Patients: From the FIRST Registry - https://doi.org/10.3899/jrheum.201135 Tanaka, et al: Effects of Denosumab in Japanese Patients With Rheumatoid Arthritis Treated With Conventional Antirheumatic Drugs: 36-month Extension of a Phase III Study - https://doi.org/10.3899/jrheum.201376 Ye, et al: Measuring Physical Function in Psoriatic Arthritis: Comparing the Multidimensional Health Assessment Questionnaire to the Health Assessment Questionnaire–Disability Index - https://doi.org/10.3899/jrheum.200927 Concha, et al: Changes in Treatments and Outcomes After Implementation of a National Universal Access Program for Juvenile Idiopathic Arthritis - https://doi.org/10.3899/jrheum.210011 Meara, et al: A Case of Chilblains-like Lesions Post SARS-CoV-2 Vaccine? - https://doi.org/10.3899/jrheum.210226 Liu: Serum Uric Acid: A Murderer or Bystander for Cardiac-related Mortality? - https://doi.org/10.3899/jrheum.210695 Berard and Batthish: Addressing Healthcare Quality in Juvenile Idiopathic Arthritis With a Universal Access Program - https://doi.org/10.3899/jrheum.210658 October 2021 Featured articles:​ Safy-Khan, et al: Current Smoking Negatively Affects the Response to Methotrexate in Rheumatoid Arthritis in a Dose-responsive Way, Independently of Concomitant Prednisone Use - https://doi.org/10.3899/jrheum.200213 Mease, et al: Comparison of Men and Women With Axial Spondyloarthritis in the US-based Corrona Psoriatic Arthritis/Spondyloarthritis Registry - https://doi.org/10.3899/jrheum.201549 Feher, et al: Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography/Computed Tomography in Patients With Systemic Sclerosis - https://doi.org/10.3899/jrheum.210040 Mohajer, et al: Metabolic Syndrome and Osteoarthritis Distribution in the Hand Joints: A Propensity Score Matching Analysis From the Osteoarthritis Initiative - https://doi.org/10.3899/jrheum.210189 Fernández-Ávila, et al: Impact of COVID-19 Pandemic on Rheumatology Practice in Latin America - https://doi.org/10.3899/jrheum.201623https://doi.org/10.3899/jrheum.201623 Gilvaz et al: A Case of Disseminated Cutaneous Mycobacterium chelonae Infection During Treatment With Tofacitinib - https://doi.org/10.3899/jrheum.200730 Jansen, et al: Smoking and Methotrexate Inefficacy in Rheumatoid Arthritis: What About Underlying Molecular Mechanisms? - https://doi.org/10.3899/jrheum.210217 Leung: Gender Differences in Disease Activity and Impact in Axial Spondyloarthritis - https://doi.org/10.3899/jrheum.210564​ September 2021 Featured articles:​ Myasoedova, et al: Improved Incidence of Cardiovascular Disease in Patients With Incident Rheumatoid Arthritis in the 2000s: A Population-based Cohort Study - https://doi.org/10.3899/jrheum.200842 Karmacharya, et al: Diagnostic Delay in Psoriatic Arthritis: A Population-based Study - https://doi.org/10.3899/jrheum.201199 Clément, et al: Real-world Risk of Relapse of Giant Cell Arteritis Treated With Tocilizumab: A Retrospective Analysis of 43 Patients - https://doi.org/10.3899/jrheum.200595 Master, et al: Joint Association of Moderate-to-vigorous Intensity Physical Activity and Sedentary Behavior With Incident Functional Limitation: Data From the Osteoarthritis Initiative - https://doi.org/10.3899/jrheum.201250 Sheth et al: Improving Pneumococcal Vaccination Rates in Rheumatology Patients by Using Best Practice Alerts in the Electronic Health Records - https://doi.org/10.3899/jrheum.200806 Bathon: Is the Gap in Incidence of Cardiovascular Events in Rheumatoid Arthritis Really Closing? - https://doi.org/10.3899/jrheum.210366 Villiger: Giant Cell Arteritis: Real-life Experience - https://doi.org/10.3899/jrheum.210334 Gazitt, et al: Spinal Stenosis Caused by Calcinosis in a Patient With Systemic Sclerosis - https://doi.org/10.3899/jrheum.201389 De Boer and Goekoop: Posttraumatic Chylous Knee Effusion - https://doi.org/10.3899/jrheum.191050 August 2021 Featured articles:​ Vu, et al: Impact of Comorbid Conditions on Healthcare Expenditure and Work-related Outcomes in Patients With Rheumatoid Arthritis - https://doi.org/10.3899/jrheum.200231 Taylor, et al: A Phase III Randomized Study of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, for Active Ankylosing Spondylitis - https://doi.org/10.3899/jrheum.201088 Falasinnu, et al: The Problem of Pain in Systemic Lupus Erythematosus: An Explication of the Role of Biopsychosocial Mechanisms - https://doi.org/10.3899/jrheum.200595 Hazlewood, et al: Canadian Rheumatology Association Recommendation for the Use of COVID-19 Vaccination for Patients With Autoimmune Rheumatic Diseases - https://doi.org/10.3899/jrheum.210288 Aljaberi et al: Maintaining Hepatitis B Protection in Immunocompromised Pediatric Rheumatology and Inflammatory Bowel Disease Patients - https://doi.org/10.3899/jrheum.200283 Bechman, et al: The COVID-19 Vaccine Landscape: What a Rheumatologist Needs to Know - https://doi.org/10.3899/jrheum.210106 Rahman: Why Do Patients With Systemic Lupus Erythematosus Suffer Pain? - https://doi.org/10.3899/jrheum.210057 Awqati, et al: Ulcerative Paraneoplastic Dermatomyositis in the Setting of Positive Transcriptional Intermediary Factor 1-γ Antibody - https://doi.org/10.3899/jrheum.200399 Shinoda, et al: Widespread Mechanic’s Hands in Antisynthetase Syndrome With Anti-OJ Antibody - https://doi.org/10.3899/jrheum.201043 July 2021 Featured articles:​ Pathi, et al: The Rheumatoid Arthritis Gene Expression Signature Among Women Who Improve or Worsen During Pregnancy: A Pilot Study - https://doi.org/10.3899/jrheum.201128 Stovall, et al: Relation of NSAIDs, DMARDs, and TNF Inhibitors for Ankylosing Spondylitis and Psoriatic Arthritis to Risk of Total Hip and Knee Arthroplasty - https://doi.org/10.3899/jrheum.200453 Mehta, et al: Giant Cell Arteritis and COVID-19: Similarities and Discriminators. A Systematic Literature Review - https://doi.org/10.3899/jrheum.200766 Widdifield, et al: Feminization of the Rheumatology Workforce: A Longitudinal Evaluation of Patient Volumes, Practice Sizes, and Physician Remuneration - https://doi.org/10.3899/jrheum.201166 Bachiller-Corral et al: Risk of Severe COVID-19 Infection in Patients With Inflammatory Rheumatic Diseases - https://doi.org/10.3899/jrheum.200755 Ornetti, et al: Perforating Rheumatoid Nodule Mimicking Malignant Soft-tissue Mass of the Forearm - https://doi.org/10.3899/jrheum.201290 Guillaune-Czitrom, et al: A Recurrent Central Band Keratopathy in a Child - https://doi.org/10.3899/jrheum.200462 June 2021 Featured articles:​ Xie, et al: Benefits of Methotrexate Use on Cardiovascular Disease Risk Among Rheumatoid Arthritis Patients Initiating Biologic Disease-modifying Antirheumatic Drugs - https://doi.org/10.3899/jrheum.191326 Jørgensen, et al: Relation Between Fatigue and ACR Response in Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitor Therapy: A Population-based Cohort Study - https://doi.org/10.3899/jrheum.191107 Dominguez, et al: Relationship Between Genetic Risk and Age of Diagnosis in Systemic Lupus Erythematosus - https://doi.org/10.3899/jrheum.200002 Coffey, et al: Hospitalization Rates Are Highest in the First 5 Years of Systemic Sclerosis: Results From a Population-based Cohort (1980–2016) - https://doi.org/10.3899/jrheum.200737 Singh and Cleveland: Hospitalized Infections in People With Osteoarthritis: A National US Study - https://doi.org/10.3899/jrheum.191383 May 2021 Featured articles:​ Ozen, et al: The Risk of Cardiovascular Events Associated With Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis - doi.org/10.3899/jrheum.200265 Ogdie, et al: Descriptive Comparisons of the Effect of Apremilast and Methotrexate Monotherapy in Oligoarticular Psoriatic Arthritis: The Corrona Psoriatic Arthritis/Spondyloarthritis Registry Results - doi.org/10.3899/jrheum.191209 Kim, et al: Lupus Low Disease Activity State Achievement Is Important for Reducing Adverse Outcomes in Pregnant Patients With Systemic Lupus Erythematosus - doi.org/10.3899/jrheum.200802 Mossel, et al: Clinical Phenotyping of Primary Sjögren Syndrome Patients Using Salivary Gland Ultrasonography: Data From the RESULT Cohort - doi.org/10.3899/jrheum.200482 Panwar et al: Whole-body MRI Quantification for Assessment of Bone Lesions in Chronic Nonbacterial Osteomyelitis Patients Treated With Pamidronate: A Prevalence, Reproducibility, and Responsiveness Study - doi.org/10.3899/jrheum.200329 April 2021 Featured articles:​ Barber, et al: Evaluating Quality of Care for Rheumatoid Arthritis for the Population of Alberta Using System-level Performance Measures - doi.org/10.3899/jrheum.200420 Liu, et al: Physical Activity and Attitudes Toward Exercise in People With Axial and Peripheral Spondyloarthritis - doi.org/10.3899/jrheum.200354 Harkey, et al: A Decline in Walking Speed Is Associated With Incident Knee Replacement in Adults With and at Risk for Knee Osteoarthritis - doi.org/10.3899/jrheum.200176 Mendel, et al: CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update - doi.org/10.3899/jrheum.200721 Gkrouzman, et al: Antiphospholipid Antibody Profile Stability Over Time: Prospective Results From the APS ACTION Clinical Database and Repository - doi.org/10.3899/jrheum.200513 March 2021 Featured articles:​ Almaghlouth, et al: Propensity Score Methods in Rare Disease: A Demonstration Using Observational Data in Systemic Lupus Erythematosus - doi.org/10.3899/jrheum.200254 Faye, et al: Risk of Adverse Outcomes in Hospitalized Patients With Autoimmune Disease and COVID-19: A Matched Cohort Study From New York City - doi.org/10.3899/jrheum.200989 Grosse, et al: Evaluation of Bone Erosions in Rheumatoid Arthritis: The Ultrasound Score for Erosions Versus the Modified Sharp/van der Heijde Score for Erosions - doi.org/10.3899/jrheum.200286 Liew, et al: Cardiovascular Risk Scores in Axial Spondyloarthritis Versus the General Population: A Cross-sectional Study - doi.org/10.3899/jrheum.200188 van Leeuwen, et al: Association Between Centromere- and Topoisomerase-specific Immune Responses and the Degree of Microangiopathy in Systemic Sclerosis - doi.org/10.3899/jrheum.191331 February 2021 Featured articles:​ Kiltz, et al: Ixekizumab Improves Functioning and Health in the Treatment of Radiographic Axial Spondyloarthritis: Week 52 Results from 2 Pivotal Studies - doi.org/10.3899/jrheum.200093 Sarabia, et al: The Pattern of Musculoskeletal Complaints in Patients With Suspected Psoriatic Arthritis and Their Correlation With Physical Examination and Ultrasound - doi.org/10.3899/jrheum.190857 te Kampe, et al: Sex Differences in the Clinical Profile Among Patients With Gout: Cross-sectional Analyses of an Observational Study - doi.org/10.3899/jrheum.200113 Walscheid, et al: Enthesitis-related Arthritis: Prevalence and Complications of Associated Uveitis in Children and Adolescents From a Population-based Nationwide Study in Germany - doi.org/10.3899/jrheum.191085 Master, et al: Does the 1-year Decline in Walking Speed Predict Mortality Risk Beyond Current Walking Speed in Adults With Knee Osteoarthritis? - doi.org/10.3899/jrheum.200259 January 2021 Featured articles:​ Fisher, et al: Tofacitinib Persistence in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study - doi.org/10.3899/jrheum.191252 Thomas, et al: Tumor Necrosis Factor Inhibitor Monotherapy Versus Combination Therapy for the Treatment of Psoriatic Arthritis: Combined Analysis of European Biologics Databases - doi.org/10.3899/jrheum.190815 Blaja, et al: The Challenge of Very Early Systemic Sclerosis: A Combination of Mild and Early Disease? - doi.org/10.3899/jrheum.190976 Zhai, et al: Phenylalanine Is a Novel Marker for Radiographic Knee Osteoarthritis Progression: The MOST Study - doi.org/10.3899/jrheum.200054 Koppikar, et al: Improving Hydroxychloroquine Dosing and Toxicity Screening at a Tertiary Care Ambulatory Center: A Quality Improvement Initiative - doi.org/10.3899/jrheum.191265 December 2020 Featured articles:​ Foers, et al: Circulating Small Noncoding RNA Biomarkers of Response to Triple Disease-modifying Antirheumatic Drug Therapy in White Women With Early Rheumatoid Arthritis - doi.org/10.3899/jrheum.191012 Wade, et al: Serum MicroRNA Signature as a Diagnostic and Therapeutic Marker in Patients with Psoriatic Arthritis - doi.org/10.3899/jrheum.190602 Schwartz, et al: Utility of the Brief Illness Perception Questionnaire to Monitor Patient Beliefs in Systemic Vasculitis - doi.org/10.3899/jrheum.190828 Correll, et al: Identifying Research Priorities among Patients and Families of Children with Rheumatic Diseases Living in the United States - doi.org/10.3899/jrheum.190934 Bitar, et al: Five-year Evolution Patterns of Physical Activity and Sedentary Behavior in Patients with Lower-limb Osteoarthritis and Their Sociodemographic and Clinical Correlates - doi.org/10.3899/jrheum.190854 November 2020 Featured articles:​ Cañete, et al: Expert Consensus on a Set of Outcomes to Assess the Effectiveness of Biologic Treatment in Psoriatic Arthritis: The MERECES Study - doi.org/10.3899/jrheum.191056 Aguirre, et al: Using Process Improvement and Systems Redesign to Improve Rheumatology Care Quality in a Safety Net Clinic - doi.org/10.3899/jrheum.190472 Stern, et al: Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis - doi.org/10.3899/jrheum.190945 Langlois, et al: Rituximab and Cyclophosphamide in Antisynthetase Syndrome–related Interstitial Lung Disease: An Observational Retrospective Study - doi.org/10.3899/jrheum.190505 Moore, et al: Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus - doi.org/10.3899/jrheum.190875 October 2020 Featured articles:​ Pappas, et al: Effectiveness of Tocilizumab in Patients with Rheumatoid Arthritis Is Unaffected by Comorbidity Burden or Obesity: Data from a US Registry - doi.org/10.3899/jrheum.190282 van Bentum, et al: The Ankylosing Spondylitis Performance Index: Reliability and Feasibility of an Objective Test for Physical Functioning - doi.org/10.3899/jrheum.191063 Walsh, et al: Measuring Outcomes in Psoriatic Arthritis: Comparing Routine Assessment of Patient Index Data and Psoriatic Arthritis Impact of Disease - doi.org/10.3899/jrheum.190219 Liang, et al: Hemophagocytic Lymphohistiocytosis: Prevalence, Risk Factors, Outcome, and Outcome-related Factors in Adult Idiopathic Inflammatory Myopathies - doi.org/10.3899/jrheum.190542 Kelly, et al: Scope of Outcomes in Trials and Observational Studies of Interventions Targeting Medication Adherence in Rheumatic Conditions: A Systematic Review - doi.org/10.3899/jrheum.190726 September 2020 Featured articles:​ Kuettel, et al: Pain and Self-reported Swollen Joints Are Main Drivers of Patient-reported Flares in Rheumatoid Arthritis: Results from a 12-month Observational Study - doi.org/10.3899/jrheum.190760 Ben-Shabat, et al: Mortality among Patients with Giant Cell Arteritis: A Large-scale Population-based Cohort Study - doi.org/10.3899/jrheum.190927 Tselios, et al: Advanced Chronic Kidney Disease in Lupus Nephritis: Is Dialysis Inevitable? - doi.org/10.3899/jrheum.191064 Putman, et al: The Quality of Randomized Controlled Trials in High-impact Rheumatology Journals, 1998–2018 - doi.org/10.3899/jrheum.191306 Loef, et al: Health-related Quality of Life in Patients with Hand Osteoarthritis from the General Population and the Outpatient Clinic - doi.org/10.3899/jrheum.190781 July 2020 Featured articles:​ Harrold, et al: Longterm, Real-world Safety of Adalimumab in Rheumatoid Arthritis: Analysis of a Prospective US-based Registry - doi.org/10.3899/jrheum.190260 Bakewell,et al: Imaging Techniques: Options for the Diagnosis and Monitoring of Treatment of Enthesitis in Psoriatic Arthritis - doi.org/10.3899/jrheum.190512 Hoge, et al: Association of Poverty Income Ratio with Physical Functioning in a Cohort of Patients with Systemic Lupus Erythematosus - doi.org/10.3899/jrheum.190991 Dai, et al: Sleep Quality Is Related to Worsening Knee Pain in Those with Widespread Pain: The Multicenter Osteoarthritis Study - doi.org/10.3899/jrheum.181365 Aydin, etla: The Relationship Between Physical Examination and Ultrasonography of Large Entheses of the Achilles Tendon and Patellar Tendon Origin - doi.org/10.3899/jrheum.190169 back to top June 2020 Featured articles:​ Sepriano, et al: Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort - doi.org/10.3899/jrheum.190303 Zardin-Moraes, et al: Prevalence of Psoriatic Arthritis Patients Achieving Minimal Disease Activity in Real-world Studies and Randomized Clinical Trials: Systematic Review with Metaanalysis - doi.org/10.3899/jrheum.190677 Desbois, et al: Rituximab-associated Vasculitis Flare: Incidence, Predictors, and Outcome - doi.org/10.3899/jrheum.190076 Bollhalder, et al: Magnetic Resonance Imaging Followup of Temporomandibular Joint Inflammation, Deformation, and Mandibular Growth in Juvenile Idiopathic Arthritis Patients Receiving Systemic Treatment - doi.org/10.3899/jrheum.190168 Colaco, et al: Predictive Utility of Cardiovascular Risk Prediction Algorithms in Inflammatory Rheumatic Diseases: A Systematic Review - doi.org/10.3899/jrheum.190261 May 2020 Featured articles:​ Skougaard, et al: ELECTOR: eHealth in rheumatology - doi.org/10.3899/jrheum.181362 Lee, et al: Cesarean births in AS - doi.org/10.3899/jrheum.190754 Quinn, et al: Exercise echocardiography in SSc - doi.org/10.3899/jrheum.190226 Gibson, et al: FM assessment screenting tool - doi.org/10.3899/jrheum.190277 Qendro, et al: Immunization in rheumatic diseases - doi.org/10.3899/jrheum.181376 April 2020 Featured articles:​ Keystone, et al: Primary/secondary nonresponse to anti-TNF - doi.org/10.3899/jrheum.190102 Singh and Cleveland: Insurance, income, and TSA outcomes - doi.org/10.3899/jrheum.190287 Mukwikwi, et al: SLE retinal complications - doi.org/10.3899/jrheum.181102 Rosato, et al: SSc renal parenchymal thickness - doi.org/10.3899/jrheum.190165 Elfishawi, et al: Changes in incident gout - doi.org/10.3899/jrheum.190346 Cron and Chatham: The Rheumatologist’s Role in COVID-19 - doi.org/10.3899/jrheum.200334 Peschken: Possible Consequences of a Shortage of Hydroxychloroquine for Lupus Patients Amid the COVID-19 Pandemic - doi.org/10.3899/jrheum.200395 Putman and Ruderman: Learning from Adversity: Lessons from the COVID-19 Crisis - doi.org/10.3899/jrheum.200411 March 2020 Featured articles:​ Agca, et al: CV risk in RA - doi.org/10.3899/jrheum.180726 Perruccio, et al: PASDAS and MDA in PsA - doi.org/10.3899/jrheum.181472 Bruschi, et al: NET in SLE/lupus nephritis - doi.org/10.3899/jrheum.181232 Cook, et al: Statins and revision arthroplasty - doi.org/10.3899/jrheum.180574 Singh, et al: Effectiveness of allopurinol in gout - doi.org/10.3899/jrheum.190522 February 2020 Featured articles:​ Jamal, et al: Adverse events and cancer immunotherapy - doi.org/10.3899/jrheum.190084 Ormseth, et al: Plasma miRNA RA panel - doi.org/10.3899/jrheum.181029 Rostami, et al: AS risk prediction - doi.org/10.3899/jrheum.181209 de Vries-Bouwstra, et al: Recommendation agreement in SSc - doi.org/10.3899/jrheum.181173 Bowes, et al: Automated cartilage segmentation - doi.org/10.3899/jrheum.180541 back to top January 2020 Featured articles:​ Bechman, et al: Placebo response in RA - doi.org/10.3899/jrheum.190008 Yusuf: Editorial - doi.org/10.3899/jrheum.190900 Walsh, et al: axSpA identification methods - doi.org/10.3899/jrheum.181005 Urowitz, et al: AVE in SLE in decades - doi.org/10.3899/jrheum.180986 Ying, et al: VA SSc stroke risk - doi.org/10.3899/jrheum.181311 Mills, et al: Rheumatic diseases and pregnancy - doi.org/10.3899/jrheum.181067 Author Interviews Q & A: Catherine Bakewell, MD, Sibel Zehra Aydin, MD, Lihi Eder, MD, PhD, and Gurjit S. Kaeley, MBBS, MRCP, RhMSUS Editor-in-Chief Dr. Earl Silverman speaks with Dr. Catherine Bakewell from the Intermountain Healthcare Medical Group Salt Lake Clinic, Dr. Sibel Zehra Aydin from the University of Ottawa, Dr. Lihi Eder at the Women’s College Hospital, and Dr. Gurjit S. Kaeley from the University of Florida about their and their co-authors' review article "Imaging Techniques: Options for the Diagnosis and Monitoring of Treatment of Enthesitis in Psoriatic Arthritis". For the full article: Imaging Techniques: Options for the Diagnosis and Monitoring of Treatment of Enthesitis in Psoriatic Arthritis by Catherine Bakewell, Sibel Zehra Aydin, Veena K. Ranganath, Lihi Eder and Gurjit S. Kaeley. [Read the full transcript.] For the video interview: Viewing Rheum Q & A: Daniel K. White, PT, ScD, MSc Editor-in-Chief Dr. Earl Silverman speaks with Dr. Daniel K. White from the University of Delaware about his and his co-authors' editorial "Walk At Least 10 Minutes a Day for Adults With Knee Osteoarthritis: Recommendation for Minimal Activity During the COVID-19 Pandemic". For the full article: Walk At Least 10 Minutes a Day for Adults With Knee Osteoarthritis: Recommendation for Minimal Activity During the COVID-19 Pandemic by Jason T. Jakiela, Esther J. Waugh, and Daniel K. White. [Read the full transcript.] For the video interview: Viewing Rheum Q & A: Dr. Roberto Caricchio, MD Editor-in-Chief Dr. Earl Silverman speaks with Dr. Roberto Caricchio from Lewis Katz School of Medicine, Temple University about his and his co-author's letter Rheumatologists and Pulmonologists at Temple University Weather the COVID-19 Storm Together. For the full article: Rheumatologists and Pulmonologists at Temple University Weather the COVID-19 Storm Together by Roberto Caricchio and Gerard J. Criner. [Read the full transcript.] For the video interview: Viewing Rheum Q & A: Drs. Michael S. Putman, MD, and Eric M. Ruderman, MD Editor-in-Chief Dr. Earl Silverman speaks with Drs. Michael S. Putman and Eric M. Ruderman from Northwestern University about their editorial Learning from Adversity: Lessons from the COVID-19 Crisis. For the full article: Learning from Adversity: Lessons from the COVID-19 Crisis by Michael S. Putman and Eric M. Ruderman. [Read the full transcript.] For the video interview: Viewing Rheum Q & A: Drs. Rosie Scuccimarri, MD, Evelyn Sutton, MD, and Mary-Ann Fitzcharles, MB, ChB Editor-in-Chief Dr. Earl Silverman speaks with Drs. Rosie Scuccimarri from McGill University, Evelyn Sutton from Dalhousie University, and Mary-Ann Fitzcharles from McGill University about their editorial Hydroxychloroquine: A Potential Ethical Dilemma for Rheumatologists during the COVID-19 Pandemic. For the full article: Hydroxychloroquine: A Potential Ethical Dilemma for Rheumatologists during the COVID-19 Pandemic by Rosie Scuccimarri, Evelyn Sutton, and Mary-Ann Fitzcharles. [Read the full transcript.] For the video interview: Viewing Rheum back to top Audio Abstracts Dr. James T. Rosenbaum For the full article: The Effect of HLA-B27 on Susceptibility and Severity of Covid-19 by James T. Rosenbaum, Hedley Hamilton, Michael H. Weisman, John D. Reveille, Kevin L. Winthrop, and Dongseok Choi. [Read the full transcript.] Dr. Niv Ben-Shabat, BMSc For the full article: Mortality among Patients with Giant Cell Arteritis: A Large-scale Population-based Cohort Study by Niv Ben-Shabat, Shmuel Tiosano, Ora Shovman, Doron Comaneshter, Yehuda Shoenfeld, Arnon D. Cohen and Howard Amital Dr. Gisele Vajgel, MD For the full article: Effect of a Single Apolipoprotein L1 Gene Nephropathy Variant on the Risk of Advanced Lupus Nephritis in Brazilians by Gisele Vajgel, Suelen Cristina Lima, Diego Jeronimo S. Santana, Camila B.L. Oliveira, Denise Maria N. Costa, Pamela J. Hicks, Maria Alina G.M. Cavalcante, Carl D. Langefeld, Lucila Maria Valente, Sergio Crovella, Gianna Mastroianni Kirsztajn, Barry I. Freedman and Paula Sandrin-Garcia Dr. Paula Muilu, MD For the full article: Opioid Use among Patients with Early Inflammatory Arthritides Compared to the General Population by Paula Muilu, Vappu Rantalaiho, Hannu Kautiainen, Lauri Juhani Virta and Kari Puolakka. [Read the full transcript.] Dr. Marie Skougaard, MD For the full article: Patients with Rheumatoid Arthritis Acquire Sustainable Skills for Home Monitoring: A Prospective Dual-country Cohort Study (ELECTOR Clinical Trial I) by Marie Skougaard, Henning Bliddal, Robin Christensen, Karen Ellegaard, Sabrina M. Nielsen, Jakub Zavada, Sabina Oreska, Niels S. Krogh, Christian C. Holm, Merete L. Hetland, Jiri Vencovsky, Henrik Røgind, Peter C. Taylor and Henrik Gudbergsen. [Read the full transcript.] back to top Techniques Dr. Edward C. Keystone, MD, FRCP(C) For the full article: The Dorsal 4-finger Technique: A Novel Method to Examine Metacarpophalangeal Joints in Patients with Rheumatoid Arthritis by Mohammed A. Omair, Pooneh Akhavan, Ali Naraghi, Shikha Mittoo, Juan Xiong, Deborah Weber, Daming Lin, Melissa Weber, and Edward C. Keystone. [Read the full transcript.] back to top Contents Author Interviews Audio Abstracts Techniques Editor's Picks Archives Author Interviews Audio Abstracts Editor's Picks 2019 Editor's Picks 2018