Adalimumab TNFa antagonists

Several pro-inflammatory cytokines, such as TNFa, IL-1, IL-6, are important in the initiation and maintenance of various autoimmune diseases, such as RA, CD, and psoriasis. Thus, targeted therapies, which have been developed to inhibit their activity, have resulted in clinical improvement of these patients. Currently, there are three TNFa inhibitors (etanercept, infliximab, and adalimumab) and one IL-1 receptor antagonist (anakinra) that have been approved for the treatment of at least one of these diseases. In addition, a number of other anti-cytokine therapies are in clinical development. The TNFa antagonists will be reviewed here. 

Cardiovascular A 51-year-old woman with relapsing polychondritis presented with acute myocarditis 2 weeks after a second course of adalimumab. Cardiac arrest followed within a few hours with autopsy showing necrotising eosinophilic myocarditis. This appears to be the first report of a TNFa antagonist associated with this condition [74 ]. 

Respiratory TNFa antagonists may be of benefit in the treatment of advanced or refractory sarcoidosis, a multisystem granulomatous inflammatory disease of unknown aetiology but, paradoxically, a sarcoidosis-like reaction may sometimes occur with TNFa blockade. A sarcoid-like reaction with pulmonary symptoms occurred in a patient with psoriatic arthritis soon after the initiation of adalimumab. lATthdrawal of the mAb and antiinflammatory therapy with corticosteroids resulted in resolution of the pulmonary symptoms [75 ]. 

Five TNF antagonists are currently approved for the treatment of RA, etanercept (ETN), infliximab (INF), adalimumab (ADA), golimumab (GOL), and certolizumab pegol (CZP). ETN, a fusion protein of two identical chains of the recombinant human TNF receptor, p75, fused with the Fc portion of human IgGl, binds to soluble TNFa in vivo. INF, ADA, and GOL are all monoclonal antibodies to TNF-a INF is chimeric while ADA and GOL are fully humanized. CZP is a human anti-TNF Fab fragment that is conjugated with polyethylene glycol. 

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