Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease‐Modifying Antirheumatic Drug Treatment

Abstract

ObjectiveWe undertook this phase III study to evaluate baricitinib, an orally administered JAK‐1/JAK‐2 inhibitor, as monotherapy or combined with methotrexate (MTX) compared to MTX monotherapy in patients with active rheumatoid arthritis (RA) who had received no or minimal conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) and who were naive to biologic DMARDs.MethodsA total of 588 patients were randomized 4:3:4 to receive MTX monotherapy (once weekly), baricitinib monotherapy (4 mg once daily), or the combination of baricitinib and MTX for 52 weeks. The primary end point assessment was a noninferiority comparison of baricitinib monotherapy to MTX monotherapy based on the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 24.ResultsThe study met its primary objective. Moreover, baricitinib monotherapy was found to be superior to MTX monotherapy at week 24, with a higher ACR20 response rate (77% versus 62%; P ≤ 0.01). Similar results were observed for combination therapy. Compared to MTX monotherapy, significant improvements in disease activity and physical function were observed for both baricitinib groups as early as week 1. Radiographic progression was reduced in both baricitinib groups compared to MTX monotherapy; the difference was statistically significant for baricitinib plus MTX. The rates of serious adverse events (AEs) were similar across treatment groups, while rates of some treatment‐emergent AEs, including infections, were increased with baricitinib plus MTX. Three deaths were reported, all occurring in the MTX monotherapy group. Malignancies, including nonmelanoma skin cancer, were reported in 1 patient receiving MTX monotherapy, 1 receiving baricitinib monotherapy, and 4 receiving baricitinib plus MTX.ConclusionBaricitinib alone or in combination with MTX demonstrated superior efficacy with acceptable safety compared to MTX monotherapy as initial therapy for patients with active RA.

Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials

“…Safety observations for all patients treated with one or more dose of assigned study drug were analysed by assigned treatment until time of rescue (all studies), time of switch (RA-BEAM only) or completion of the treatment period (all studies). Statistical analyses for the Japanese subgroups were conducted as previously described for the overall populations of each study [18][19][20][21], but without adjustment for multiplicity. Importantly, none of the studies were designed to provide adequate power for between-treatment comparisons in any subgroup, including that of the subgroup of Japanese patients.…”

“…Results for the overall populations of each study are published elsewhere [18][19][20][21]. The studies were phase 3, multicenter, randomized, double-blind, placebo/ active-controlled trials.…”

“…Four global phase 3 trials of baricitinib that cover all stages of the RA treatment continuum, from patients who were DMARD-naïve to those who had failed multiple csDMARDs or bDMARDs, have been conducted: RA-BEGIN, RA-BEAM, RA-BUILD, and RA-BEACON [18][19][20][21]. In RA-BEGIN, the study population was patients with no or minimal prior csDMARD and no prior bDMARD or tsDMARD treatment.…”

Baricitinib: a new oral treatment for rheumatoid arthritis

“…7 The primary endpoint was the American College of Rheumatology 20% response (ACR20, a 20% reduction in scores for joints, pain, patient and investigator assessments, and disability). A fourth trial, RA BEGIN, 8 was conducted in patients with little or no prior treatment with DMARDs; they were not selected because a conventional DMARD was unsuitable and therefore they do not fall within the licensed indications.…”

The 2016 Eular Guidelines for the Diagnosis and Treatment of Early Arthritis

“…В то же время материалы систематического обзора рандо-мизированных контролируемых исследований (РКИ) по-зволил сделать «парадоксальный» вывод о том, что более высокая эффективность ГИБП в комбинации с МТ, по сравнению с монотерапией МТ, может быть частично связана с использованием недостаточно адекватных доз МТ и таблетированной формы, а не более эффективной подкожной формы этого препарата [58]. Монотерапия ингибиторами Янус-киназы (JAK) эффективнее моноте-рапии МТ [59,60]. Однако и в этих исследованиях боль-шинство больных получали неадекватную дозу МТ (око-ло 15 мг/нед) и только в таблетированной форме.…”