The Janus kinase (JAK)-1 and 2 inhibitor baricitinib effectively inhibited progression of radiographic joint damage in patients with moderate to severely active adult-onset rheumatoid arthritis (RA), according to a study published in Annals of the Rheumatic Diseases.
Data were derived from RA-BUILD, a multicenter phase 3 randomized, double-blind, placebo-control trial (ClinicalTrials.gov Identifier: NCT01721057) that evaluated the efficacy of baricitnib in patients with RA and a previous inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).
High Yield Data Summary
- Selective inhibition of JAK1 and JAK2 with baricitinib resulted in clinical improvements in RA symptoms and inhibited joint structural disease progression in patients with active RA who have failed csDMARDs
Patients eligible for inclusion into the RA-BUILD study were diagnosed with RA according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria for the Classification of RA.
Moderate to severely active RA was defined by the presence of at least 6/68 tender joints and at least 6/66 swollen joints, with a history of insufficient response, contraindication, or intolerance to a csDMARD. All study participants were biologic disease-modifying antirheumatic drug (bDMARD)-naïve.
Study participants were then randomly assigned 1:1:1 to receive once daily doses of baricitinib 2 mg (n=229), 4mg (n=227), or placebo (n=228), stratified by both region and whether joint erosions were present on baseline screening radiographs.
Patients with estimated glomerular filtration rate ≥40 and <60 mL/min/1.73 m2 received the lower baricitinib 2 mg dose. Concomitant stable doses of csDMARDs, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, and corticosteroids were permitted to be taken. Patients who were randomly assigned to receive placebo were re-evaluated at week 16, and participants who are nonresponders were rescued with baricitinib 4 mg administered orally, once daily through week 24.
The primary outcome measure was the proportion of study participants who achieved American College of Rheumatology 20% Improvement (ACR20) at week 12. Secondary outcome measures included changes from baseline to week 12 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores and Disease Activity Score 28-Joint Counts (DAS-28).
Additional secondary outcome measures included changes in patient reported outcomes from baseline to week 24, and proportion of study participants achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response at week 24.
A total of 684 patients were randomly assigned to the 3 treatment arms. Primary ACR20 response rates was significantly improved for those receiving baricitinib 4mg as compared with those receiving placebo (62% vs 39%, P < .001).
Patients receiving baricitinib 4mg were also found to have improvements in all major secondary outcome measures, with improvements noted from baseline to week 12 in HAQ-DI, DAS28 C-Reactive protein, worst tiredness, and worst joint pain compared with placebo.
Notably, patients receiving eitherbaricitinib 2mg and 4mg demonstrated a reduction in radiographic structural joint damage from baseline to week 24 compared with placebo. Study participants receiving baricitnib 4mg further had reduced degrees in radiographic progression in both total score and erosion and joint space narrowing component scores compared with placebo.
Serious adverse events (SAEs) were similar among both baricitinib treatment groups and placebo. One report of tuberculosis was noted in a patient receiving baricitinib 4mg. Another patient was observed to have a nonmelanoma cutaneous malignancy while receiving baricitnib 4mg. Baricitinib treatment was also associated with lower absolute neutrophil counts and increases in both low-density and high-density lipoprotein.
Summary and Clinical Applicability
In patients with moderate to severely active RA who had failed prior treatment with or have interollance to csDMARDs, baricitinib resulted in improvements in ACR20 scores and and inhibited structural progression of radiographic joint damage at 24-weeks.
“Importantly, a beneficial treatment effect was observed in all baricitinib-treated, analysed subgroups, irrespective of concomitant csDMARD use… [demonstrating] a short-term symptomatic benefit of baricitinib, but the radiographic progression data indicate a beneficial effect on joint damage,” the study authors stated. Results from the clinical trial suggest that JAK1 and JAK 2 inhibition with baricitinib is an effective DMARD in adult patients with moderate to severelly active RA.
Limitations and Disclosures
The NCT01721057 clinical trial was funded by Eli Lilly and Company, the manufacturer of baricitinib.
Dougados M, Van der heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2016 Sep 29. doi:10.1136/annrheumdis-2016-210094 [Epub ahead of print]