RA Patients Improve with Baricitinib at 12 Weeks

Once daily baricitinib for rheumatoid arthritis has led to significant clinical improvements for patients who failed conventional synthetic DMARDs, a new study shows.

French researchers writing in a September edition of the Annals of the Rheumatic Diseases describe the results from the 2012 RA-BUILD study, a phase III double-blind investigation into the efficacy of baricitinib, an oral Janus kinase 1 and 2 inhibitor, for adult patients with severe rheumatoid arthritis.

Maxime Dougados, the corresponding author, and colleagues describe how, despite the use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), many patients continue to display active disease or intolerance of therapy.

Baricitinib is an oral inhibitor of Janus kinase (JAK) 1 and 2, which are enzymes that mediate the release of inflammatory cytokines responsible for rheumatoid arthritis related inflammation. The efficacy of baricitinib in phase II trials has led to the phase III trials:  RA-BEYOND and RA-BUILD trials. Patients in the RA-BUILD study suffered from moderate to severe rheumatoid arthritis who were not responding to or could not tolerate conventional therapy.

Patients in the study were adults with active rheumatoid arthritis, tender swollen joints, elevated C-reactive protein and poor response or intolerance to more than or equal to 1 conventional disease-modifying anti-rheumatic drug. Patients were excluded if they had taken a biologic or had significant comorbidities.

The majority of patients had received ≥2 prior csDMARDs. Most were receiving background methotrexate (MTX), either alone (49%) or in combination with another csDMARD (23%). Approximately, 16% were receiving a single non-MTX csDMARD. Some patients (7%) were receiving no concomitant DMARD.

In the trial, 684 patients were randomized to receive doses of placebo (228 patients), baricitinib 2 mg (229 patients) or 4 mg daily (227 patients). The study lasted 24 weeks with the primary outcome measurement being how many patients achieved an American College of Rheumatology 20% response (ACR20).

At 12 weeks, 4 mg baricitinib was more effective than placebo in achieving American College of Rheumatology 20% (ACR20) response endpoint (62% compared to 39% placebo). Statistically significant improvements in secondary measures were observed in disease activity scores for 28 joint count C-reactive protein levels (DAS28-CRP), simplified disease activity indices (SDAI), health assessment questionnaire-disability index (HAQ-DI), worst tiredness and worst joint pain reports. Finally, when compared to placebo, there was a statistically significant reduction in radiographic progression of structural joint damage at 24 weeks with both doses of baricitinib.

Adverse events were similar across all three treatment groups and were rare - 5% for baricitnib 4 mg and 3% for baricitinib 2 mg. One patient had tuberculosis (baricitinib 4 mg) and one had non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred in the placebo group. Infection was the most common adverse event across all three groups but affected 2% or less of participants.

Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein.

The study was limited by a short duration and inability to compare the two dose regimens for statistical difference. It was also noted that a large percentage of placebo patients achieved the ACR20 response (39%), which is of undetermined significance by the authors. 

The authors conclude that the results of the RA-BUILD study suggest, “Baricitinib is an effective disease-modifying agent for treating the signs and symptoms of RA.” The higher dose of 4 mg appears to be the most effective dose.

Disclosures:

This study was funded by Eli Lilly and Company and Incyte Corporation.

References:

Dougados M, Heijde D, Chen Y, et al.  Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis 2016;0:1–8. doi:10.1136/annrheumdis-2016-210094