A nationwide Swedish cohort study found Janus kinase inhibitors demonstrate slightly better pain reduction outcomes compared to tumor necrosis factor inhibitors in patients with rheumatoid arthritis, particularly among those previously treated with multiple biologic disease-modifying antirheumatic drugs.
The study, published in Arthritis & Rheumatology, provides real-world evidence on the comparative effectiveness of Janus kinase inhibitors (JAKis) and various biologic disease-modifying antirheumatic drugs (bDMARDs) on pain outcomes in rheumatoid arthritis (RA) patients.
Researchers analyzed data from 11,387 treatment episodes involving 8,430 patients who initiated treatment with a JAKi (n=1,827), tumor necrosis factor inhibitors (TNFis) (n=6,422), interleukin-6 inhibitor (IL-6i) (n=887), abatacept (n=1,102), or rituximab (n=1,149) between 2017 and 2019. The study used information from several linked Swedish national registers, including the Swedish Rheumatology Quality Register.
The study compared differences in change in pain, assessed with a VAS (0-100 mm), from baseline to 3 months, as well as proportions of patients remaining on initial treatment with low pain (VAS pain <20) at 12 months. Comparisons of treatment responses between JAKis and bDMARDs were evaluated using multivariable linear regression, adjusted for patient characteristics, comorbidities, current co-medication, and previous treatment.
In fully adjusted models, JAKis decreased pain scores by 4.0 mm more than TNFis and by 3.9 mm more than rituximab at 3 months. There were no statistically significant differences between JAKis and abatacept or IL-6is.
Subgroup analyses revealed JAKis were particularly effective when used as third line of treatment or later. In first-line treatment, IL-6is showed significantly greater pain reduction than JAKis at 3 months. For second-line treatment, JAKis decreased pain significantly more at 3 months compared to both TNFis and rituximab. In third-line or later treatment, JAKis showed significantly better pain outcomes compared to TNFis at both 3 and 12 months.
JAKi monotherapy also showed better outcomes than TNFi monotherapy, with adjusted mean differences for JAKi monotherapy of 5.4 mm at 3 months and 5.5% higher response rate at 12 months compared to TNFi monotherapy.
At 12 months, 67% of patients in the JAKi group were still on treatment, compared to 58% for IL-6is and 80% for rituximab. Among those with VAS pain <20 at 12 months, the proportion in remission was lower and the fraction with active disease higher in the JAKi group compared to the TNFi group.
The median age was 61 years for the JAKi group and 59 years for the TNFi group. Female patients comprised 81.9% of the JAKi group and 78.1% of the TNFi group. Median symptom duration was 13.2 years for the JAKi group and 8.1 years for the TNFi group. RF seropositivity was observed in 75.6% of the JAKi group and 70.3% of the TNFi group.
The study had a significant amount of missing data, particularly for follow-up evaluations. The researchers note that VAS pain values were missing for about 30% of patients at baseline and 50-60% of patients at 12 months. Multiple imputation was used to address this issue. Additionally, the majority of patients were treated with baricitinib, potentially limiting generalizability to other JAKis.
Conflict of interest disclosures were not made available at time of publishing.