Immunology and Biotherapies

KeywordsAdverse reactions; Cytokines; Monoclonal antibodies; Bone morphogenic proteins;Colony-stimulating factors; Interferons; Interleukins; Tumor necrosis factor alfa;Adalimumab; Certolizumab; Etanercept; Golimumab; Infliximab; Abciximab;Alemtuzumab; Bevacizumab; Cetuximab; Daclizumab; Natalizumab; Ranibizumab;Rituximab; Tocilizumab; Trastuzumab

Via Krishan Maggon

Abstract

While for a century therapeutics has been dominated by small molecules, i.e. organic chemicals of ~400Da absorbable via the gut, this is no longer the case. There are now a plethora of important medicines which are proteins and injectable, which have dramatically improved the therapy of many inflammatory diseases and of cancer. Most of these are monoclonal antibodies, some are receptor Ig Fc fusion proteins, others are cytokines or enzymes. The key to this new aspect of therapeutics has been the filling of unmet needs, and the consequent commercial success, which promoted further research and development. The first ‘biologic’ for a common disease, rheumatoid arthritis (RA), was a monoclonal antibody, infliximab, to human tumour necrosis factor (TNF). This was based on our work, which is described in this review, summarizing how TNF was defined as a good target in RA, how it was developed is described here, as well as future indications for anti-TNF and related agents. Biologics are now the fastest growing sector of therapeutics.

Via Krishan Maggon

SummaryBackground

One-third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti-TNFs do not respond to treatment, and a relevant proportion experience loss of response or intolerance.

Aim

To investigate the efficacy and safety of a second anti-TNF agent after primary/secondary failure or intolerance to a first drug.

Methods

Inclusion criteria: studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab-pegol (CZP) as the second anti-TNF in CD or UC. Search strategy: Bibliographical searches (PubMed/Embase). Data synthesis: percentage of response/remission; the meta-analysis was performed using the inverse variance method.

Results

We included 46 studies (37 CD, 8 UC, 1 pouchitis). The CD studies comprised 32 switching IFXADA, 4 IFXCZP and 1 ADAIFX. Overall, the second anti-TNF after the failure of IFX in CD induced remission in 43% and response in 63% of patients. The remission rate was higher when the reason to withdraw the first anti-TNF was intolerance (61%) than after secondary (45%) or primary failure (30%); response rates were, respectively, 72%, 62% and 53%. All UC studies switched IFXADA, six of them reporting remission rates ranging from 0% to 50%. Adverse events rate ranged from 0% to 81% in CD, most of them mild (serious adverse event 0–21%, discontinuation rate <20%).

Conclusions

The efficacy of a second anti-TNF in CD patients largely depends on the cause for switching. The remission rate is higher when the reason to withdraw the first anti-TNF is intolerance (61%), compared with secondary (45%) or primary failure (30%). Further studies of switch ADAIFX are needed to evaluate this strategy. PROSPERO-registry-number: CRD42014012943.

Via Krishan Maggon

(2014). Physicochemical characterization of Remsima®. mAbs: Vol. 6, No. 5, pp. 1163-1177. doi: 10.4161/mabs.32221

Via Krishan Maggon