EFFICACY AND SAFETY OF TOFACITINIB MODIFIED-RELEASE 11 MG ONCE DAILY PLUS METHOTREXATE IN RHEUMATOID ARTHRITIS PATIENTS WITH AN INADEQUATE RESPONSE TO METHOTREXATE: OPEN-LABEL PHASE RESULTS FROM A GLOBAL PHASE 3B/4 METHOTREXATE WITHDRAWAL STUDY
Objectives:
- To describe the first global clinical study (ORAL Shift; NCT02831855) of the tofacitinib modified-release 11 mg once-daily formulation in patients with rheumatoid arthritis.
- To report the efficacy, patient-reported outcomes, and safety of tofacitinib modified-release 11 mg once daily plus methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate over the 24-week open-label phase of ORAL Shift.
Introduction:
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The tofacitinib modified-release (MR) 11 mg once-daily (QD) formulation was first approved in the US in 2016 for the treatment of patients with moderate to severe RA and an inadequate response or intolerance to methotrexate (MTX). ORAL Shift is the first global study of tofacitinib MR 11 mg QD plus MTX. Efficacy, patient-reported outcomes (PROs), and safety from the open-label (OL) phase of ORAL Shift are reported here.
Methods:
ORAL Shift (NCT02831855) was a global Phase 3b/4 study in patients aged ≥18 years with moderate to severe RA and an inadequate response to MTX. Patients received OL tofacitinib MR 11 mg QD plus MTX (tofacitinib plus MTX) for 24 weeks; those achieving low disease activity (LDA; Clinical Disease Activity Index [CDAI] ≤10) at Week (W)24 entered the 24-week double-blind MTX withdrawal phase, where the primary endpoint was assessed (data reported elsewhere).[1] Outcomes from the OL phase, reported descriptively here, include: mean change from baseline to W12 and W24 in disease activity measures and PROs; rates of American College of Rheumatology (ACR) and Health Assessment Questionnaire-Disability Index (HAQ-DI) response, and LDA and remission, at W12 and W24 (see Table 1); and safety (see Table 2).
Results:
In the OL phase, 694 patients received tofacitinib plus MTX. Most patients were female (76.7%), white (85.6%), with a mean age of 56.8 years and mean RA duration of 8.8 years. At W24 (end of the OL phase), 526 (75.8%) patients achieved CDAI-defined LDA (Table 1). In the OL phase, Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) improved with mean (standard deviation) changes from baseline of -1.96 (1.19) and -2.67 (1.25) at W12 and W24, respectively (Table 1). Mean changes from baseline at W12 and W24 showed improvements in all other efficacy outcomes and PROs (Table 1). ACR20/50/70 and HAQ-DI response rates, and LDA and remission rates, improved from W12 to W24 (Table 1). Adverse events (AEs), serious AEs, and discontinuations due to AEs were reported by 52.2%, 2.9%, and 5.9% of patients, respectively; no deaths were reported (Table 2). The most common AEs were nasopharyngitis and upper respiratory tract infection. AEs of special interest each occurred in ≤1% of patients (Table 2).
Discussion:
Tofacitinib MR 11 mg QD plus MTX improved disease activity and PROs in patients with moderate to severe RA and an inadequate response to MTX. No new safety risks were observed. Efficacy and safety in this OL phase appeared consistent with that of tofacitinib immediate-release 5 mg twice daily [2] and with the double-blind phase of ORAL Shift.[1]
1. Cohen SB et al. Lancet Rheumatol 2019; 1: E23-E34.
2. Bird P et al. J Clin Rheumatol 2019; 25: 115-126.
3. Felson DT et al. Arthritis Rheum 2011; 63: 573-586.
Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Jennifer Arnold, PhD, of CMC Connect and funded by Pfizer Inc.