Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study

Abstract

Introduction: To evaluate long-term efficacy of once-daily baricitinib 2 mg in patients with active rheumatoid arthritis who had an inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or biologic DMARDs (bDMARD).

Methods: Data from patients treated with baricitinib 2 mg daily in two 24-week, phase III studies, RA-BUILD (csDMARD-IR; NCT01721057) and RA-BEACON (bDMARD-IR; NCT01721044), and one long-term extension study (RA-BEYOND; NCT01885078), were analyzed (120 weeks). The main outcomes were achievement of low-disease activity (LDA; Simple Disease Activity Index [SDAI] ≤ 11), clinical remission (SDAI ≤ 3.3), Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5 and improvement from baseline of ≥ 0.22, and safety. Analysis populations included (1) all patients and (2) never-rescued patients. Completer and non-responder imputation (NRI) analyses were conducted on each population.

Results: In RA-BUILD, 684 were randomized (229 to baricitinib 2 mg, 180 of whom completed RA-BUILD and entered RA-BEYOND). In RA-BEACON, 527 were randomized (174 to baricitinib 2 mg, 117 of whom completed RA-BEACON and entered RA-BEYOND). In RA-BUILD-BEYOND, 85.1% (63/74, completer) and 27.5% (63/229, NRI) of csDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 40.5% (30/74, completer) and 13.1% (30/229, NRI) were in SDAI remission; 62.2% (46/74, completer) and 20.1% (46/229, NRI) had HAQ-DI ≤ 0.5 and 81.1% (60/74, completer); and 26.2% (60/229, NRI) achieved ≥ 0.22 change from baseline at week 120. In RA-BEACON-BEYOND, 86.5% (32/37, completer) and 18.4% (32/174, NRI) of bDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 24.3% (9/37, completer) and 5.2% (9/174, NRI) were in SDAI remission; 50.0% (19/38, completer) and 10.9% (19/174, NRI) had HAQ-DI ≤ 0.5; and 73.7% (28/38, completer) and 16.1% (28/174, NRI) achieved ≥ 0.22 change from baseline at week 120. Rates of adverse events of special interest were consistent with previous reports.

Conclusions: Long-term treatment with baricitinib 2 mg demonstrated efficacy for up to 120 weeks and was well tolerated.

Trial registration: ClinicalTrials.gov identifier, NCT01721057, NCT01721044, and NCT01885078.

Keywords: Arthritis; Baricitinib; Rheumatoid.

Figures

Fig. 1

The treatment course is described for both originating studies. aPatients enrolled in RA-BUILD had an inadequate response or intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drugs (DMARD) and had not previously been treated with a biologic DMARD; bPatients enrolled in RA-BEACON had an inadequate response to prior treatment with ≥ 1 tumor necrosis factor inhibitor and were on stable doses of concomitant conventional DMARD therapy; cRescue treatment (baricitinib 4 mg) was assigned at week 16 for non-responders (patients whose tender and swollen joint counts had improved by less than 20% from baseline at both week 14 and week 16). After week 16, rescue was at the discretion of the investigator based on tender and swollen joint counts. Patients who completed RA-BUILD or RA-BEACON and who were receiving baricitinib 2 mg and 4 mg continued blinded treatment in the long-term extension (LTE) study. Treatment was switched to open-label baricitinib 4 mg once patients were rescued or switched from placebo upon entry to the LTE study. Please note, the focus of this manuscript was the treatment course of baricitinib 2 mg, shown in light blue; dRescue therapy was available for patients with a Clinical Disease Activity Index score > 10 at 3 months or later following the study entry; eTotal duration of the ongoing LTE study, RA-BEYOND, is 7 years

Fig. 2

The patient disposition for RA-BUILD describes the frequency and reasons for discontinuation in the originating study and in the long-term extension study. The percentages are calculated based on the overall modified intention-to-treat patients included in the originating study

Fig. 3

The patient disposition for RA-BEACON describes the frequency and reasons for discontinuation in the originating study and in the long-term extension study. The percentages are calculated based on the overall modified intention-to-treat patients included in the originating study

Fig. 4

Patients who achieved Simple Disease Activity Index ≤ 11 in RA-BUILD and RA-BEACON trials. a, b The efficacy over time based on the non-responder imputation (NRI) and completer analysis in RA-BUILD. c, d The efficacy over time based on the NRI and completer analysis in RA-BEACON

Fig. 5

Patients who achieved Simple Disease Activity Index ≤ 3.3 in RA-BUILD and RA-BEACON trials. a, b The efficacy over time based on the non-responder imputation (NRI) and completer analysis in RA-BUILD. c, d The efficacy over time based on the NRI and completer analysis in RA-BEACON

Fig. 6

Patients who reached Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤ 0.5 in RA-BUILD and RA-BEACON trials. a, b The percent of patients who met or exceeded HAQ-DI ≤ 0.5 at week 120 based on the non-responder imputation (NRI) and completer analysis in RA-BUILD. c, d The percent of patients who met or exceeded HAQ-DI ≤ 0.5 at week 120 based on the NRI and completer analysis in RA-BEACON

Fig. 7

Patients who achieved Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement ≥ 0.22 in RA-BUILD and RA-BEACON trials. a, b The efficacy over time based on the non-responder imputation (NRI) and completer analysis in RA-BUILD. c, d The efficacy over time based on the NRI and completer analysis in RA-BEACON