Costimulation blockade in rheumatic diseases: where we are?

PURPOSE OF REVIEW: To describe the mechanisms of action of abatacept (CTLA4-Ig) and summarize the evidence of its efficacy and safety in rheumatoid arthritis (RA) and other rheumatic diseases such as juvenile idiopathic arthritis (JIA).

RECENT FINDINGS: Several studies have demonstrated the clinical efficacy (disease activity, quality of life, prevention of structural damage) of abatacept in patients with RA who have failed to respond to standard disease-modifying antirheumatic drugs (DMARDs) and antitumour necrosis factor-alpha biologic agents. Selective modulation of T-cell costimulation may also be an alternative therapy for children with JIA who are resitant to conventional DMARDs or biologics.

SUMMARY: T-cell activation is critical to the onset and maintenance of RA. Abatacept (CTLA4-Ig), the first selective T-cell costimulation modulator has shown to be effective in RA and JIA. Recent 2-year data from the 'AIM' trial suggests an increased and sustained effect of blocking of T cell signalling on the inhibition of RA structural damage progression over time. Abatacept's safety profile in combination with DMARDs also seems to be favourable but should be avoided in combination with other biologics.