Impact of baseline body mass index on the efficacy and safety of tofacitinib in patients with psoriatic arthritis

Abstract

Objectives: This post-hoc analysis explored the impact of body mass index (BMI) on tofacitinib efficacy/safety in patients with active psoriatic arthritis (PsA).

Methods: Data were pooled from two phase 3 studies (NCT01877668; NCT01882439). Analyses included patients randomised to tofacitinib 5/10 mg twio times a day or placebo, stratified by baseline BMI: <25 kg/m², ≥25-<30 kg/m², ≥30-<35 kg/m² or ≥35 kg/m². Endpoints (month 3): American College of Rheumatology (ACR20/50/70), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Psoriasis Area and Severity Index (PASI) 75 response rates; dactylitis/enthesitis resolution rates; changes from baseline Short Form-36 Health Survey version 2 (SF-36v2) Physical/Mental Component Summary (PCS) scores and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score. Safety was also reported.

Results: Analysis included 710 patients; 43.8% were obese (BMI ≥30 kg/m²). Tofacitinib demonstrated higher efficacy response rates at month 3, compared with placebo, regardless of baseline BMI. Generally, ACR20/50/70 and HAQ-DI response rates, enthesitis resolution rates and changes from baseline in SF-36v2 PCS score and FACIT-F total score (month 3) were reduced in patients with baseline BMI ≥35 kg/m² versus patients with lower BMIs. Elevated alanine aminotransferase/aspartate aminotransferase levels were reported in patients with baseline BMI ≥35 kg/m² receiving tofacitinib 5 mg but not 10 mg two times a day.

Conclusion: Tofacitinib demonstrated greater efficacy than placebo in patients with PsA, regardless of baseline BMI. For all treatment arms, reduced efficacy was observed in patients with baseline BMI ≥35 kg/m². Safety was generally comparable across BMI categories, although the effect of tofacitinib on liver enzymes in patients with baseline BMI ≥35 kg/m² was inconclusive.

Keywords: arthritis; autoimmune diseases; inflammation; psoriatic.

Figure 1

Response rates at month 3 for (A) ACR20,* (B) ACR50,* (C) ACR70,* (D) HAQ-DI† and (E) PASI75‡ by baseline BMI category and treatment group (pooled data from OPAL Broaden and OPAL Beyond). N indicates the number of patients with non-missing BMI evaluable at month 3; n indicates the number of responders. All patients received a stable dose of one csDMARD throughout each study. *ACR20/50/70 response rates were defined as the proportions of patients achieving a ≥20/50/70% improvement from baseline in tender and swollen joint counts and ≥20/50/70% improvement from baseline in three of the five remaining ACR core measures. †HAQ-DI response rate was defined as the proportion of patients achieving a reduction from baseline HAQ-DI of ≥0.35, considered the minimum clinically important difference. ‡PASI75 response rate was defined as the proportion of patients achieving a reduction from baseline PASI of ≥75%, assessed only in patients with baseline BSA ≥3% and a baseline PASI>0. ACR20/50/70, American College of Rheumatology≥20/50/70% response criteria; BID, two times a day; BMI, body mass index; BSA, body surface area; csDMARD, conventional synthetic disease-modifying antirheumatic drug; HAQ-DI, Health Assessment Questionnaire-Disability Index; PASI75, ≥75% Psoriasis Area and Severity Index improvement from baseline.

Figure 2

Resolution rates at month 3 for (A) dactylitis* and (B) enthesitis† by baseline BMI category and treatment group (pooled data from OPAL Broaden and OPAL Beyond). N indicates the number of patients with non-missing BMI evaluable at month 3; n indicates the number of responders. All patients received a stable dose of one csDMARD throughout each study. *Dactylitis resolution rates, defined as the absence of dactylitis in all of the 20 assessed digits, assessed only in patients with baseline DSS >0. †Enthesitis resolution rates, defined as the absence of enthesitis in all of the six assessed sites, assessed only in patients with baseline LEI >0. BID, two times a day; BMI, body mass index; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DSS, Dactylitis Severity Score; LEI, Leeds Enthesitis Index.

Figure 3

LS mean (SE) changes from baseline at month 3 in (A) SF-36v2 PCS score, (B) SF-36v2 MCS score, (C) FACIT-F total score and (D) HAQ-DI by baseline BMI category and treatment group (pooled data from OPAL Broaden and OPAL Beyond). N indicates the number of patients with non-missing BMI evaluable at month 3; n indicates the number of responders. All patients received a stable dose of one csDMARD throughout each study. Δ, change from baseline; BID, two times a day; BMI, body mass index; csDMARD, conventional synthetic disease-modifying antirheumatic drug; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least squares; MCS, Mental Component Summary; PCS, Physical Component Summary; SF-36v2, Short Form-36 Health Survey version 2.