Tofacitinib, peficitinib touted as top treatments for refractory RA

The Janus kinase (JAK) inhibitors tofacitinib 10 mg and peficitinib 150 mg prove to be the most effective regimens in the treatment of patients with refractory rheumatoid arthritis (RA) receiving methotrexate (MTX), without increasing the risk of serious adverse events, according to the results of a network meta-analysis.

“As patients with RA may receive tofacitinib or peficitinib if they are refractory or intolerant to or contraindicated by disease‐modifying antirheumatic drugs (DMARDs), it is important to determine the optimal treatment methods,” the investigators said.

The network meta‐analysis included 15 pairwise comparisons—six of which were direct comparisons of seven interventions—from nine randomized controlled trials. The total population comprised 3,836 active RA patients with an inadequate DMARD response (1,887 for efficacy-related and 1,428 for safety-related events). Quality of the trials was high, with Jadad scores between 3 and 5.

Used in combination with MTX, all doses of JAK inhibitors showed a more favourable effect on the American College of Rheumatology (ACR)20 response compared with placebo (odds ratio [OR] values: 4.20 for tofacitinib 10 mg; 4.07 for peficitinib 150 mg; 3.68 for tofacitinib 5 mg; and 2.63 for peficitinib 100 mg). Notably, the efficacy of tofacitinib 10 mg (OR, 1.43), peficitinib 150 mg (OR, 1.39), and tofacitinib 5 mg (OR, 1.25) tended to be greater than that of adalimumab. [Int J Rheum Dis 2020;doi:10.1111/1756-185X.13854]

Based on surface under the cumulative ranking curve analysis (SUCRA), tofacitinib 10 mg+MTX (SUCRA score, 0.760) had the greatest probability of being the best treatment to induce ACR20. This was followed by peficitinib 150 mg+MTX (SUCRA score, 0.730), tofacitinib 5 mg+MTX (SUCRA score, 0.640), adalimumab+MTX (SUCRA score, 0.484), and peficitinib 100 mg+MTX (SUCRA score, 0.378).

In terms of safety, serious adverse events (SAEs) tended to occur less frequently with peficitinib 150 mg+MTX, adalimumab+MTX, placebo+MTX, and peficitinib 100 mg+MTX than with tofacitinib 10 mg+MTX and tofacitinib 5 mg+MTX.

“Nonetheless, the number of SAEs was not significantly different among the six treatments, suggesting comparable safety among the different tofacitinib and peficitinib regimens,” the investigators noted.

The following regimens were ranked according to their safety profile: peficitinib 150 mg+MTX (SUCRA score, 0.816), adalimumab+MTX (SUCRA score, 0.729), and placebo+MTX (SUCRA score, 0.675). These were  followed by peficitinib 100 mg+MTX (SUCRA score, 0.411), tofacitinib 10 mg+MTX (SUCRA score, 0.207), and tofacitinib 5 mg+MTX (SUCRA score, 0.163).

“The results … were consistent with previous meta-analyses and indicated that treatment with tofacitinib and peficitinib resulted in a statistically substantial improvement on the basis of the ACR20 response criteria,” according to the investigators. [Korean J Int Med 2014;29:656; Clin Drug Invest 2019;40:65-72]

“However, our network meta-analysis is different from previous meta-analyses, as we were able to generate a ranking order of the relative effectiveness and safety of tofacitinib and peficitinib treatments in patients with active RA,” they added.

Recent studies of RA treatment have focused on small molecules that can inhibit intracellular kinases (such as those in the JAK pathways), given that some patients with an inadequate response to MTX and administered biological (b)DMARDs do not respond adequately to these therapies and show poorer responses with subsequent bDMARD treatment. [N Engl J Med 2000;343:1594-1602]

Tofacitinib is a JAK inhibitor approved for use in RA, while peficitinib is used in Japan and is undergoing evaluation for FDA approval. The relative efficacy and safety of these two drugs should be assessed in long-term studies, as follow-up in most of the trials only lasted 3 or 6 months, the investigators said.