Biologics or Tofacitinib for People with Rheumatoid Arthritis Unsuccessfully Treated with Biologics

Summary

A Cochrane review [Abstract] 1 included 12 studies with a total of 3 364 subjects. The review studied the effects of biologics on people with rheumtoid arthritis (RA), whose previous treatment with biologic therapy was unsuccessful, either due to lack of benefits or occurrence of side effects, or both. Data were available for 4 TNF-biologics (certolizumab pegol 1 study, n=37; etanercept 3 studies, n=348; golimumab 1 study, n=461; infliximab 1 study, n=27), 3 non-TNF biologics (abatacept 3 studies, n=632; rituximab 2 studies, n=1019; tocilizumab 2 studies, n=589), and 1 study for tofacitinib (n=399). The comparator was placebo in 3 studies (n=548), methotrexate (MTX) or other traditional disease-modifying anti-rheumatic drugs (DMARD) in 6 studies (n=2468), and another biologic in 3 studies (n=348). The majority of the studies (10/12) lasted less than 12 months. There were no published data for the comparison of tofacitinib monotherapy versus placebo.

Biologic monotherapy versus placebo: Compared to placebo, biologics were associated with clinically meaningful and statistically significant improvement in RA as demonstrated by higher ACR50 (RR 4.10, 95% CI 1.97 to 8.55; NNTB 8, 95% CI 4 to 23; 3 studies, n=548) and RA remission rates (RR 13.51, 95% CI 1.85 to 98.45; NNTB 11, 95% CI 3 to 136; 1 study, n=389). Results for withdrawals due to adverse events and serious adverse events did not show any statistically significant or clinically meaningful differences. Biologic + MTX versus active comparator (MTX/other traditional DMARDs): Compared to MTX/other traditional DMARDs, biologic + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50 (RR 4.07, 95% CI 2.76 to 5.99; NNTB 7, 95% CI 5 to 11; 3 studies, n=1 479), function measured by HAQ (an improvement with a MD of 0.29, 95% CI 0.21 to 0.36; NNTB 5, 95% CI 4 to 7; 2 studies, n=959), and RA remission rates (RR 20.73, 95% CI 4.13 to 104.16; NNTB 17, 95% CI 4 to 96; 2 studies, n=959) in direct comparisons. Results were not clinically meaningful or statistically significantly different for withdrawals due to adverse events or serious adverse events, and were inconclusive for cancer.Tofacitinib + MTX versus active comparator (MTX): Compared to MTX, tofacitinib + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50 (RR 3.24, 95% CI 1.78 to 5.89; NNTB 6, 95% CI 3 to 14; 1 study, n=399), and function measured by HAQ (MD 0.27 improvement, 95% CI 0.14 to 0.39; NNTB 5, 95% CI 4 to 10; 1 study, n=399). RA remission rates were not statistically significantly different but the observed difference may be clinically meaningful (RR 15.44, 95% CI 0.93 to 256.1; 1 study, n=398). There were no statistically significant or clinically meaningful differences for withdrawals due to adverse events and serious adverse events, and results were inconclusive for cancer.