Researchers recently compared the efficacy and safety of four JAK inhibitors – for treating rheumatoid arthritis (RA) – and found no significant differences in efficacy or safety between the four medications.
More than 85% of participants remained on the medication during the six-month trial, said the team.
RA, an autoimmune and inflammatory disease, results when immune cells attack healthy tissue by mistake, usually in the joint’s lining, causing inflammation.
Available biological disease-modifying medications (bDMARDs) effectively reduce disease activity and achieve remission. However, patients receive these via IV or subcutaneous injection.
JAK (Janus kinase inhibitors, or jakinib, a type of immune modulating medication inhibiting the activity of one or more of the Janus kinase family of enzymes) are another type of RA medication that can be taken orally. They can also delay the progression of the disease.
Usually, treatment for RA starts with conventional DMARDs. If the response is not satisfactory, bDMARDs or JAK inhibitors might be recommended, which are more specific at targeting inflammatory markers and more efficient at inducing remission and low disease activity.
The researchers completed a retrospective study comparing, published in Rheumatology, showing the efficacy and safety of four JAK inhibitors for treating rheumatoid arthritis (RA):
• tofacitinib (TOFA)
• baricitinib (BARI)
• peficitinib (PEF)
• upadacitinib (UPA)
They determined no significant difference in efficacy or safety between the four JAK inhibitors they evaluated.
Study co-author Dr Shinya Hayashi of the Department of Orthopaedic Surgery at Kobe University Graduate School of Medicine, Japan, told Medical News Today:
“Several papers have demonstrated the efficacy and safety of difference among JAK inhibitors, however, those reports did not adjust to patients’ backgrounds. We first compared the efficacy of JAK inhibitors after patients’ background matching. The efficacy and safety of TOF, BAR, PEF, and UPA were not significantly different for the treatment of the patients.”
What do JAK inhibitors do for RA?
A total of 622 patients were treated at seven major university hospitals in Japan with JAK inhibitors and monitored for side effects, disease improvement, and whether they wanted to continue taking the medications.
The researchers used the Clinical Disease Activity Index, C-reactive protein value, and modified Health Assessment Questionnaire to measure the effectiveness of the medications after six months of use.
They found that roughly one in three RA patients reached remission, with three in four reaching low disease activity.
The researchers noted that after six months, more than 80% of the subjects were still on JAK inhibitor drugs. Retention rates over six months included:
• Overall – 85.4%
• TOFA – 87.4%
• BARI – 89.5%
• PEF – 82.8%
• UPA – 83%.
“Medical professionals can feel comfortable choosing JAK inhibitors if a patient failed bDMARD treatment,” Hayashi noted.
Side effects of JAK inhibitors
A small number of adverse events among patients on JAK inhibitors were reported.
The FDA’s warnings on JAK inhibitors indicate several health risks, including an increased risk of cardiovascular events, for instance:
• bacterial, viral, and fungal infections
• opportunistic infections, such as tuberculosis
• higher rate of lymphoma, lung cancer, thrombosis, pulmonary embolism, venous, and arterial thrombosis
Individual JAK inhibitors could also have additional side effects.
More research in broader RA population needed
Although the study had some notable strengths, like using real-world settings rather than controlled trials to determine the effectiveness and safety of JAK inhibitors, it had some limitations.
First, the researchers did not closely examine the link between side effects and discontinuation of the medication.
In addition, due to the small number of participants, the researchers could not generalise the results to the larger RA population.
The observational duration was only 24 weeks, and more studies with longer durations are needed.
Last, the scientists did not monitor changes in dosage during the study period.
Study details
Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study
Published in Rheumatology on 1 November 2023
Abstract
Objective
This multicentre, retrospective study compared the efficacy and safety of tofacitinib, baricitinib, peficitinib and upadacitinib in real-world clinical settings after minimising selection bias and adjusting the confounding patient characteristics.
Method
The 622 patients were selected from the ANSWER cohort database and treated with tofacitinib (TOF), baricitinib (BAR), peficitinib (PEF) or upadacitinib (UPA). The patient’s background was matched using propensity score-based inverse probability of treatment weighting (IPTW) among four treatment groups. The values of Clinical Disease Activity Index (CDAI), C-reactive protein (CRP), and modified Health Assessment Questionnaire (mHAQ) after drug initiation and the remission or low disease activity (LDA) rates of CDAI at 6 months after drug initiation were compared among the four groups. Further, the predictive factor for TOF and BAR efficacy was analysed.
Results
The retention and discontinuation rates until 6 months after drug initiations were not significantly different among the four JAK inhibitors treatment groups. Mean CDAI value, CDAI remission rate, and CDAI-LDA rate at 6 months after drug initiation were not significantly different among treatment groups. Baseline CDAI (TOFA: OR 1.09, P < 0.001; BARI: OR 1.07, P < 0.001), baseline CRP (TOFA: OR 1.32, P = 0.049), baseline glucocorticoid dose (BARI: OR 1.18, 95% CI 1.01–1.38, P = 0.035), a number of previous biological or targeted synthetic disease-modifying antirheumatic drugs (biological/targeted synthetic DMARDs) (BARI: OR 1.36, P = 0.004) were predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment.
Conclusion
The efficacy and safety of TOF, BAR, PEF and UPA were not significantly different for the treatment of patients with rheumatoid arthritis.
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