Kevzara is indicated in combination with methotrexate to treat RA, but can also be given as monotherapy when methotrexate is inappropriate or not tolerated. It is administered by subcutaneous injection using a pre-filled syringe or pen.
Sarilumab is a fully human monoclonal antibody. Like the humanised monoclonal antibody tocilizumab (RoActemra), sarilumab binds to both soluble and membrane-bound forms of the interleukin-6 (IL-6) receptor.
IL-6 is the most abundant cytokine in the serum and synovial fluid of patients with RA, and levels correlate with both disease activity and joint destruction.
The efficacy and safety of sarilumab were assessed in three randomised, double-blind studies in adults with moderately to severely active RA: MOBILITY and TARGET were placebo-controlled studies and MONARCH was an active-controlled study.
Participants in MOBILITY and TARGET were randomised to receive sarilumab 150mg, 200mg, or placebo every 2 weeks.
Add-on to methotrexate
In MOBILITY, patients with an inadequate response to methotrexate received sarilumab or placebo together with weekly methotrexate for 52 weeks.
The sarilumab 150mg and 200mg groups showed significant improvements compared with the placebo group in all three co-primary endpoints:
- American College of Rheumatology (ACR) 20% response rate at week 24 (58.0% and 66.4%, respectively, vs 33.4% [p<0.0001]
- least-squares mean change in Health Assessment Questionnaire disability index (HAQ DI) at week 16 (20.53 and 20.55, respectively, vs 20.29 [p<0.0001])
- mean change in modified Sharp/van der Heijde score of radiographic damage at week 52 (0.90 and 0.25, respectively, vs 2.78 [p<0.0001]).
Add-on to DMARDs
TARGET recruited patients with an inadequate response or intolerance to anti-tumor necrosis factor (TNF) therapy, who received sarilumab or placebo for 24 weeks together with conventional synthetic DMARDs.
Again, the sarilumab groups did better than the placebo group in terms of the two co-primary endpoints.
The ACR20 response rate at week 24 was significantly higher with sarilumab 150mg and sarilumab 200mg than with placebo (55.8% and 60.9%, respectively, vs 33.7%; p<0.0001), as was the least-squares mean change from baseline in HAQ DI score at week 12 (-0.46 [p=0.0007] and -0.47 [p=0.0004] respectively, vs -0.26).
Monotherapy versus adalimumab
The active-controlled study, MONARCH, compared sarilumab (200mg every 2 weeks) with the anti-TNF antibody adalimumab (Humira; 40mg every 2 weeks) as monotherapy for 24 weeks.
Sarilumab was superior to adalimumab with regard to the primary endpoint of change from baseline in 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) (−3.28 vs −2.20; p<0.0001).
Sarilumab-treated patients also achieved significantly higher ACR 20/50/70 response rates (p≤0.0074 for all) and experienced significantly greater improvement in HAQ-DI (p=0.0037).
The most frequent adverse reactions seen with sarilumab in clinical studies were neutropenia, increased ALT, injection site erythema, upper respiratory tract infections, and urinary tract infections. The most common serious adverse reactions were infections.
Sarilumab is contraindicated in patients with active, severe infections and treated patients should be closely monitored for signs of infections, including TB.