Tofacitinib beneficial for PsA irrespective of BMI
medwireNews: A post-hoc analysis of two phase 3 trials shows efficacy of tofacitinib in patients with psoriatic arthritis (PsA), irrespective of BMI.
Jon Giles (Columbia University Vagelos College of Physicians and Surgeons, New York, USA) and colleagues say these results “suggest that tofacitinib can still be considered an effective treatment option for patients with PsA, regardless of their BMI status.”
The post-hoc analysis of data from the previously reported OPAL Broaden and OPAL Beyond trials included 710 patients with PsA who were randomly assigned to receive tofacitinib 5 mg or 10 mg twice daily, or placebo.
The patients were stratified into four groups according to baseline BMI, including 161 who were underweight or of normal weight (<25 kg/m2), 238 who were overweight (≥25 to <30 kg/m2), 186 with class 1 obesity (≥30 to <35 kg/m2), and 125 with class 2 or 3 obesity (≥35 kg/m2).
At 3 months, the Janus kinase (JAK) inhibitor was associated with better response rates than placebo in all four BMI cohorts.
For instance, higher ACR20 response rates were reported with tocilizumab 5 mg and 10 mg versus placebo for patients in all four BMI categories. The corresponding rates were 51.1% and 62.8% versus 29.3% for underweight or normal weight patients, 49.4% and 57.1% versus 33.3% for overweight patients, 57.9% and 58.1% versus 30.0% for patients with class 1 obesity, and 52.5% and 45.0% versus 26.5% among those with class 2 or 3 obesity. The results were similar for ACR50/70 response rates.
In general, irrespective of BMI, patients given tocilizumab versus placebo had better HAQ-DI and PASI75 response rates, dactylitis and enthesitis resolution rates, and improvements from baseline in scores on the physical and mental components of the Short-Form Health Survey-36v2, Functional Assessment of Chronic Illness Therapy-Fatigue, and HAQ-DI.
However, Giles et al note in RMD Open that the response rates were “generally lower” in patients with a BMI of 35 kg/m2 or more versus the other BMI groups, and they say this was even more pronounced in those who received tofacitinib at a dose of 10 mg instead of 5 mg.
The reduced efficacy of tofacitinib in patients with class 2 or 3 obesity, alongside previous reports of similar findings with tumor necrosis factor (TNF) inhibitors, is “poorly understood,” explain the researchers, who propose that “[pharmacokinetic] properties, volume of distribution and lipophilicity may be contributing factors.”
Giles and team add: “It is also possible that, due to the inflammatory processes associated with obesity, higher doses of TNF [inhibitors] or JAK inhibitors are required to treat individuals with an elevated BMI, compared with those with lower BMIs.”
The researchers describe “no notable differences” between the safety profiles across the BMI groups of patients given tofacitinib.
In all the BMI groups, both doses of tofacitinib were associated with greater percent changes from baseline in alanine aminotransferase and aminotransferase levels compared with placebo. The greatest change in these liver enzymes was seen in patients given tofacitinib 5 mg who had grade 2 or 3 obesity, but the effect of tofacitinib on liver enzymes in this group was deemed “inconclusive” by the study investigators.
They point out that due to the post-hoc nature of their study and the short 3-month follow-up, “further research is required to evaluate the long-term impact of BMI on treatment response to tofacitinib in patients with PsA in the real world.”
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