Network meta‐analysis of tofacitinib versus biologic treatments in moderate‐to‐severe rheumatoid arthritis patients

Abstract

What is known and objective Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by inflammation and pain in the joints. Tofacitinib is an oral drug recently approved for RA treatment; it inhibits Janus protein kinases (JAK) that reduces RA symptoms when conventional DMARDs do not trigger a response. This study aimed to compare the efficacy of biological DMARDs in monotherapy or combined with methotrexate in RA patients and compare the treatments. Methods We reviewed the literature for articles published up to June 2017, evaluating the efficacy and safety of the biological DMARDs indicated for RA in patients with inadequate responses to conventional DMARDs and naïve to biological DMARDs, in similar populations, considering ACR50 as the efficacy variable. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each drug combination, and these parameters were transformed into differences in responses to assess the effectiveness of the alternative medicines. Equivalence therapeutic alternatives (ETA) were ensured to assess the possibility of considering these medications with equivalent efficacy. A network meta‐analysis (NMA) was performed using Bayesian approaches and the fixed‐effects model. Results and discussion Twenty‐seven randomized clinical trials (RCTs) that met the pre‐established criteria were identified. The 95% CI of biological DMARDs was higher than that of placebo without methotrexate, except for certolizumab, golimumab‐m, anakinra‐m and adalimumab monotherapy. These DMARDs performed significantly better than the placebo, except for etanercept, certolizumab, tofacitinib and golimumab. Certolizumab‐m was better than anakinra‐m and adalimumab, and tocilizumab alone or combined with methotrexate was superior to adalimumab. Etanercept‐m yielded a higher difference in responses compared with the other biological DMARDs, which presented more homogeneous responses, except for adalimumab and anakinra‐m, which yielded worse results. None of the biological DMARDs displayed ETA to etanercept‐m; however, they displayed ETA with certolizumab‐m, except for adalimumab and anakinra‐m. What is new and conclusion All biological DMARDs used in combination with methotrexate, except for etanercept, anakinra, certolizumab and tocilizumab without methotrexate, were displayed ETA on using ACR50 at week 24 in patients naïve to biological DMARDs. Etanercept displayed a greater difference in responses, although the high uncertainty of the comparative results prevented the confirmation of the increased efficacy of this drug.

Efficacy and safety of NI-0101, an anti-toll-like receptor 4 monoclonal antibody, in patients with rheumatoid arthritis after inadequate response to methotrexate: a phase II study

“…In general, the NI-0101 treatment group showed similar or worse responses than the placebo group at week 12. Moreover, the improvements noted were lower than observed when other targeted DMARDs (biologics or small molecules) have been added to therapy in MTX-IR patients with RA 34 35. Despite clinical improvement in both treatment groups, there was no significant reduction from baseline in CRP, an objective measure of inflammation, for patients receiving either placebo or NI-0101 added to MTX.…”

Tofacitinib Persistence in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study

“…Approved by the U.S. Food and Drug Administration in November 2012 (2), tofacitinib is a relatively new medication, and evidence of its effectiveness and safety is based mainly on randomized clinical trials (RCTs). The efficacy and safety of tofacitinib were shown to be comparable with, or non-inferior to, the bDMARDs in RCTs of 6-24 months (3)(4)(5)(6) and in network meta-analyses (7,8).…”

“…Nevertheless, persistence is affected by other factors, such as out-of-pocket costs (14,15) and prescriber preference (16). Based on the evidence that RA patients prefer oral medications over subcutaneous and intravenous medications (17), and that efficacy reported in RCTs is similar for tofacitinib and bDMARDs (4)(5)(6)(7)(8), it is reasonable to expect that patients taking tofacitinib would adhere to treatment longer than patients taking bDMARDs. However, mounting evidence shows that adherence during the implementation phase is often worse with tofacitinib (18)(19)(20).…”

Efficacy and safety of tofacitinib for immune-mediated inflammatory rheumatic diseases (Part I)

“…Эффективность и приемлемая безопасность ТОФА, сравнимая с ГИБП, подтверждена в серии метаанализов [152][153][154][155][156][157][158][159][160][161][162]. В нескольких метаанализах Cochrane оценивались эффективность (ACR50, динамика HAQ, частота ремиссии, рентгенологическое прогрессирование деструкции суставов) и безопасность комбинированной терапии ГИБП и ТОФА и монотерапии этими препаратами у пациентов с недостаточным эффектом МТ или других БПВП и ГИБП.…”