Study Finds Greater Pain Reduction With JAKis Over bDMARDs in Third-Line RA

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New research has found that Janus kinase inhibitors (JAKis) had a slightly better effect on pain in patients with rheumatoid arthritis (RA), compared with tumor necrosis factor inhibitors (TNFis), with patients who had previously been treated with at least 2 biologic disease-modifying anti-rheumatic drugs (bDMARDs) experiencing the greatest differences. JAKis also had similar pain reduction effects to other, non TNFi-bDMARDs.¹

“So far, only limited results are available from observational studies comparing the effectiveness of JAKis and bDMARDs on pain reduction in clinical practice, especially when it comes to non-TNFi bDMARDs,” lead investigator Anna Eberhard, MD, PhD candidate, Rheumatology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden, and colleagues wrote.¹

Eberhard and colleagues analyzed data from patients with RA starting treatment with a JAKi (n = 1827), TNFi (n = 6422), IL-6 inhibitor (n = 887), abatacept (n=1102) or rituximab (n = 1149) in 2017-2019, from several linked Swedish national registers, in a retrospective study. They assessed differences between treatments in change in pain with a visual analogue scale (VAS; 0-100 mm), from baseline to 3 months, and the proportions of patients remaining on initial treatment with low pain (VAS pain <20) at 12 months. They used multivariable linear regression, adjusted for patient characteristics, comorbidities, current co-medication and previous treatment, to compare treatment responses between JAKis and bDMARDs.¹

“In particular, it has been reported that JAKis may have a special impact on pain.² Specifically, in the RA-BEAM and SELECT-COMPARE trials, treatment with baricitinib and upadacitinib, respectively, resulted in greater pain reduction compared with adalimumab,” Eberhard and colleagues wrote.¹

The investigators found that JAKi treatment was associated with a greater decrease in pain at 3 months compared with TNFi treatment (adjusted mean additional decrease, 4.0 mm [95% CI,1.6-6.3]), with similar findings in comparison to other non-TNFi bDMARDs. More patients achieved low pain at 12 months on JAKis compared with TNFis, especially among those previously treated with at least 2 bDMARDs (adjusted change contrast, 5.3% [95% CI 1.0-9.6]). They found no significant differences between pain responses in patients starting bDMARD/targeted synthetic monotherapy or combination therapy with conventional synthetic DMARDs.¹

Of patients treated with JAKis, 20% remained on drug and reached low pain at 12 months from baseline, while this proportion ranged from 17% (IL-6) to 26% (rituximab) for patients on bDMARDs. After adjustment, there were numerically higher proportions of patients remaining on JAKis with low pain than on TNFis or IL-6is, but these differences were not statistically significant. Among those with low pain at 12 months, less patients were in than among those treated with TNFis.¹

“Although differences were modest, JAKis had a slightly better effect on pain outcomes at 3 and 12 months in this study compared with TNFis, particularly in patients previously treated with at least 2 bDMARDs and when given as monotherapy. In addition, JAKis were at least as effective in reducing pain as non-TNFi bDMARDs,” Eberhard and colleagues concluded.¹

REFERENCES

1. Eberhard A, Giuseppe DD, Askling J, et al. Effectiveness of janus kinase inhibitors compared with biologic disease modifying anti-rheumatic drugs on pain reduction in rheumatoid arthritis. Arthritis Rheumatol. Published online September 22, 2024. doi.org/10.1002/art.43014

2. Harrington R, Al Nokhatha SA, Conway R. JAK Inhibitors in Rheumatoid Arthritis: An Evidence-Based Review on the Emerging Clinical Data. J Inflamm Res 2020;13:519-531. DOI:10.2147/JIR.S219586