THE EFFECTS OF JANUS KINASE INHIBITORS ON PAIN IN RHEUMATOID ARTHRITIS: SUBANALYSIS OF A NETWORK META-ANALYSIS
Author(s)
Luuk van Esveld, PharmD1, Marijke van den Dikkenberg, MSc2, Nathalie Luurssen-Masurel, PhD3, Pascal de Jong, MD PhD3, Marc R. Kok, MD PhD2, Tessa M Bosch, PharmD PhD2, Mariska Quirina Nikita Hackert, PhD2, Angelique Weel-Koenders, MSc, PhD, MD4, Deirisa Lopes Barreto, PhD2, Martijn Kuijper, PhD5.
1Researcher, Maasstad Ziekenhuis, Rotterdam, Netherlands, 2Maasstad Ziekenhuis, Rotterdam, Netherlands, 3Erasmus MC, Rotterdam, Netherlands, 4Erasmus University & Maasstad Hospital, Rotterdam, Netherlands, 5Maasstad Hospital, Rotterdam, Netherlands.
1Researcher, Maasstad Ziekenhuis, Rotterdam, Netherlands, 2Maasstad Ziekenhuis, Rotterdam, Netherlands, 3Erasmus MC, Rotterdam, Netherlands, 4Erasmus University & Maasstad Hospital, Rotterdam, Netherlands, 5Maasstad Hospital, Rotterdam, Netherlands.
OBJECTIVES: Janus kinase (JAK) inhibitors may provide additional pain reduction compared with biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) patients. Moreover, individual JAK inhibitors differ in receptor selectivity and downstream signaling profiles, which may contribute to variation in their pain‑modulating effects. However, direct evidence from head-to-head comparisons of individual JAK inhibitors on pain is lacking. Therefore, this subanalysis of a previously reported network meta-analysis (NMA) compared the effects of JAK inhibitors with each other and with adalimumab.
METHODS: This study reports a subanalysis of a previously conducted systematic review and NMA, including only studies of JAK inhibitors reporting pain outcomes using the visual analogue scale (VAS) or numeric rating scale (NRS). Random effects NMA was performed, adjusting for concomitant methotrexate use. Results were visualized using a forest plot, a triangular table comparing direct and NMA estimates, and a surface under the cumulative ranking curve (SUCRA) table to assess relative effectiveness.
RESULTS: In total, 34 studies were included, with heterogeneity ranging from low to moderate (I2 = 0-46.1%), and no evidence of inconsistency. Upadacitinib was associated with greater pain reduction than adalimumab (mean difference (MD) VAS: −5.17 mm; 95% CI: −9.53; −0.48). Among JAK inhibitors, upadacitinib also showed greater VAS pain reductions versus baricitinib (MD: −6.90 mm; 95% CI: −11.14; −2.84) and tofacitinib (MD: −4.91 mm; 95% CI: −8.01; −1.72), while the difference versus filgotinib was not statistically significant (MD: −3.72 mm; 95% CI: −7.66; 0.23). SUCRA analysis showed a high probability of upadacitinib being the most effective treatment for pain reduction (99.14%). No other significant differences among JAK inhibitors and between JAK inhibitors and adalimumab were observed.
CONCLUSIONS: Upadacitinib may offer a modest advantage in pain reduction over other JAK inhibitors and adalimumab. However, results should be interpreted cautiously due to population heterogeneity. Further research is needed to determine its clinical relevance.
METHODS: This study reports a subanalysis of a previously conducted systematic review and NMA, including only studies of JAK inhibitors reporting pain outcomes using the visual analogue scale (VAS) or numeric rating scale (NRS). Random effects NMA was performed, adjusting for concomitant methotrexate use. Results were visualized using a forest plot, a triangular table comparing direct and NMA estimates, and a surface under the cumulative ranking curve (SUCRA) table to assess relative effectiveness.
RESULTS: In total, 34 studies were included, with heterogeneity ranging from low to moderate (I2 = 0-46.1%), and no evidence of inconsistency. Upadacitinib was associated with greater pain reduction than adalimumab (mean difference (MD) VAS: −5.17 mm; 95% CI: −9.53; −0.48). Among JAK inhibitors, upadacitinib also showed greater VAS pain reductions versus baricitinib (MD: −6.90 mm; 95% CI: −11.14; −2.84) and tofacitinib (MD: −4.91 mm; 95% CI: −8.01; −1.72), while the difference versus filgotinib was not statistically significant (MD: −3.72 mm; 95% CI: −7.66; 0.23). SUCRA analysis showed a high probability of upadacitinib being the most effective treatment for pain reduction (99.14%). No other significant differences among JAK inhibitors and between JAK inhibitors and adalimumab were observed.
CONCLUSIONS: Upadacitinib may offer a modest advantage in pain reduction over other JAK inhibitors and adalimumab. However, results should be interpreted cautiously due to population heterogeneity. Further research is needed to determine its clinical relevance.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
MSR78
Topic
Methodological & Statistical Research, Patient-Centered Research
Disease
Biologics & Biosimilars, Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal)