Biologic therapies for autoimmune and inflammatory (A/I) diseases became blockbuster drugs shortly after their first approvals in the late 1990s (Remicade [infliximab], Enbrel [etanercept]) and early 2000s (Humira [adalimumab], Rituxan [rituximab]). The patent protections for these drugs ensured high global annual revenues in the $7.3bn– $16.5bn range for the recent years of 2014–16 (Medtrack, April 2017). However, as the EU and US expiration dates have approached, development activity for biosimilar competition has heated up.

The successful TNF antagonists were widely developed as therapies for some of the most prevalent A/I diseases, such as rheumatoid arthritis (RA), psoriasis (Ps), ankylosing spondylitis (ASp), and psoriatic arthritis (PsA), for which they gained approvals in global markets. Humira and Remicade are also approved for Crohn’s disease (CD) and ulcerative colitis (UC), indications for which Enbrel was not developed. Rituxan, a CD20 antagonist that transiently depletes B cells, was developed within A/I only for severe, treatment-refractory RA, following its original approval for hematological malignancies. As biosimilar development for complex biologics comes of age, this review will profile the trial activity, main sponsors, and approaches being taken to claim a share from these four hot A/I drugs in global markets.