Patients with early rheumatoid arthritis (RA) receiving treatment with baricitinib vs methotrexate (MTX) monotherapy were found to have greater and more rapid pain relief, with clinically meaningful improvements in physical health, according to study results published in RMD Open.
A phase 3, randomized, double-blind, active, comparator-controlled study (RA BEGIN; ClinicalTrials.gov Identifier: NCT01711359) was conducted to compare baricitinib with MTX in the treatment of patients with moderate to severe RA.
In the current post hoc analysis, researchers sought to evaluate speed, magnitude, and maintenance of pain improvement in patients with early RA with no prior or limited exposure to disease-modifying antirheumatic drug (DMARD) therapy. Cumulative pain and benefits in quality of life (QOL) were examined as well.
The objective of the study was to comparatively evaluate the effect size and time to attainment of clinically relevant pain improvement outcomes with baricitinib, baricitinib plus MTX, and MTX alone in 1 year, as well as to assess the improvement in QOL at the population-level during this period.
Patients enrolled in the RA-BEGIN study were aged 18 years and older and had moderate to severely active adult-onset early RA, defined according to the American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) 2010 criteria, and had received 3 or fewer prior doses of MTX. Active disease was defined as at least 6/68 tender and at least 6/66 swollen joints; serum high-sensitivity C-reactive protein of at least 3.6 mg/mL; and a seropositive finding for rheumatoid factor or anticitrullinated protein antibody.
Pain was evaluated on a 0 to 100 visual analog scale (VAS). During the 52-week period, the following were evaluated: the percentage of participants with at least 30%, at least 50%, and at least 70% improvement in pain from baseline; 20 mm or lesser (mild pain) and 10 mm or lesser (limited to no pain) on the pain VAS; and time to attain pain improvement thresholds.
A total of 588 patients in the intention-to-treat population were randomly assigned in a 4:3:4 ratio to receive MTX monotherapy (administered orally once weekly; n=210), baricitinib monotherapy (4 mg administered once daily; n=159), or baricitinib 4 mg plus MTX therapy (n=215) for 52 weeks.
Results of the study showed that patients who received baricitinib monotherapy or baricitinib plus MTX compared with those who received MTX monotherapy had a statistically significant improvement in pain from baseline (P <.001 for both baricitinib treatment groups vs MTX).
Further, a significantly greater number of patients who received baricitinib monotherapy or baricitinib plus MTX compared with those who received MTX monotherapy showed pain improvements that fulfilled clinically meaningful thresholds. At week 24, 77.9% of patients (P =.021 vs MTX) who received baricitinib monotherapy and 80.8% (P <.001 vs MTX) who received baricitinib plus MTX compared with 67.3% of participants who received MTX monotherapy had a meaningful improvement of 30% or more in pain from baseline.
In addition, a substantial improvement in pain of 50% or greater from baseline was observed in 53.5%, 67.7% (P =.004 vs MTX), and 69.7% (P <.001 vs MTX) of patients who received MTX alone, baricitinib alone, and baricitinib plus MTX, respectively. A total of 32.7%, 50.0% (P <.001 for both vs MTX), and 50.5% (P <.001 vs MTX) of patients who received MTX monotherapy, baricitinib monotherapy, and baricitinib plus MTX, respectively, achieved pain relief of at least 70% from baseline.
Baricitinib monotherapy or baricitinib plus MTX provided greater (least square mean changes [LSM] from baseline, -43 mm and -43 mm, respectively) and more rapid (median, 12 weeks and 8 weeks, respectively, to ≥70% improvement, respectively) pain relief than MTX alone (LSM, -31 mm; median, 20 weeks to ≥70% improvement) over a period of 52 weeks.
Compared with MTX alone, baricitinib administered alone or in combination with MTX provided 9 to 10 additional weeks of limited to no pain; similar gains in attainable wellness, measured using Patient Global Assessment (PtGA); and 5 to 7 additional weeks with change in Short Form Health Survey Physical Component Score (SF-36 PCS) of at least 5 over the 1-year period.
Limitations included the post hoc nature of the study; each of the study endpoints was evaluated using only a single measure; and that patient-reported symptoms may not have been consistently reported.
Overall, the researchers concluded that, “…baricitinib showed rapid and sustained improvements for pain, PtGA and SF-36 PCS compared with MTX monotherapy during this 52-week study.”
Disclosure: Some study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Taylor PC, Alten R, Álvaro Gracia JM, et al. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022;8(1):e001994. doi:10.1136/rmdopen-2021-001994