JAK inhibitors as effective as TNF, IL-6 inhibitors for rheumatoid arthritis
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Therapy discontinuance and 1-year response rates for Janus kinase and interleukin-6 inhibitors are similar to those of TNF inhibitors in patients with rheumatoid arthritis, according to data published in Annals of the Rheumatic Diseases.
“There have been several trials performed that have showed the superior efficacy of JAK inhibitors to placebo or conventional synthetic DMARDs for the treatment RA, but only in a few studies were they were compared to another second-line therapy, and only a TNF inhibitor,” Kim Lauper, MD, of Geneva United Hospitals, told Healio. “Additionally, selection criteria from randomized controlled trials are generally strict and participants are not representative of the routine clinical population.”
To evaluate the effectiveness of JAK inhibitors in the real world and compare them to other second-line RA therapies, Lauper and colleagues analyzed data from the JAK-pot collaboration, an observational study intended to evaluate biologic disease-modifying antirheumatic drugs and traditional synthetic DMARDs for RA. Patients were included from the first availability of JAK inhibitors through March 2021, and were considered eligible for the current study if they were diagnosed with RA and started treatment with a JAK inhibitor, a TNF inhibitor, an IL-6 inhibitor or abatacept (Orencia, Bristol Myers Squibb).
JAK inhibitors included in the study were baricitinib (Olumiant, Eli Lilly & Co.), tofacitinib (Xeljanz, Pfizer) or upadacitinib (Rinvoq, AbbVie). For timepoints, baseline was defined as the initiation date of each investigated therapy. Treatment course was defined as the time from initiation through discontinuation, the switch to a different therapy or the end of the study period.
The primary study outcome was treatment discontinuation. Secondary effectiveness benchmarks included reasons for discontinuation and treatment response as measured by the Clinical Disease Activity Index (CDAI).
In all, the study included 31,846 treatment courses. Among those, 17,522 were TNF inhibitors, 2,775 were abatacept, 3,863 were IL-6 inhibitors and 7,686 were JAK inhibitors. Overall discontinuation was similar across all therapies following an adjusted analysis. The “main single” reason for discontinuance was therapy ineffectiveness, Lauper and colleagues wrote.
Compared with TNF inhibitors, JAK inhibitors were less often discontinued for ineffectiveness (adjusted HR = 0.75; 95% CI, 0.67-0.83). Similarly, JAK inhibitors were discontinued due to ineffectiveness less often than IL-6 inhibitors (aHR = 0.76; 95% CI, 0.67-0.85). JAK inhibitors were discontinued for adverse events more often (aHR = 1.16; 95% CI, 1.03-1.33). Adjusted CDAI response rates were similar for JAK inhibitors, TNF inhibitors, IL-6 inhibitors and slightly lower for abatacept.
“We found that JAK-inhibitors are at least as effective as IL-6 inhibitors, TNF inhibitors or abatacept for the treatment of rheumatoid arthritis,” Lauper said. “IL-6 inhibitors and JAK inhibitors tended to be less discontinued for inefficacy, but more for adverse events. Considering similar effectiveness, but maybe slightly different profiles among these treatments, other outcomes should be considered and studied influencing treatment choice, such as patient-reported outcomes, specific safety outcomes, comorbidities, tolerability or cost-effectiveness.”
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