Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: an analysis of pooled data from phase 3 studies

Abstract

Objective: Tofacitinib is an oral Janus kinase for the treatment of rheumatoid arthritis (RA). This post hoc analysis assessed whether baseline body mass index (BMI) impacts tofacitinib efficacy in patients with RA.

Methods: Pooled data from six phase 3 studies in patients receiving tofacitinib 5 mg (N=1589) or 10 mg (N=1611) twice daily or placebo (advancing to active treatment at months 3 or 6; N=680), ±conventional synthetic disease-modifying antirheumatic drugs, were stratified by baseline BMI (<25, 25 to <30, ≥30 kg/m²). Endpoints (through to month 6) were assessed descriptively: American College of Rheumatology 20/50/70 response rates; changes from baseline (∆) in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), DAS28-4(C-reactive protein), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) and pain; and proportions of patients achieving DAS28-4(ESR) ≥1.2 and HAQ-DI ≥0.22 decreases from baseline, low disease activity (DAS28-4(ESR) ≤3.2 or CDAI ≤10) and radiographic non-progression (Δmodified Total Sharp Score ≤0.5; months 12 and 24). Estimates were adjusted using multivariable models for selected outcomes. Univariate/multivariable regression analyses determined predictors of month 6 outcomes.

Results: Of 3880 patients included, 1690 (43.6%), 1173 (30.2%) and 1017 (26.2%) had baseline BMI <25, 25 to <30 and ≥30 kg/m², respectively. Tofacitinib showed greater efficacy improvements versus placebo in each BMI category. Differences in efficacy outcomes (adjusted and unadjusted) were generally not clinically meaningful across BMI categories within treatment groups. In regression analyses, BMI was not consistently associated with selected outcomes.

Conclusions: Baseline BMI did not consistently affect tofacitinib response suggesting that tofacitinib is an effective oral treatment option for adults with moderate to severe RA regardless of baseline BMI, including patients with BMI ≥30 kg/m².

Trial registration numbers: NCT00814307, NCT01039688; NCT00960440; NCT00847613; NCT00856544; NCT00853385.

Keywords: antirheumatic agents; arthritis, rheumatoid; therapeutics.

Figure 1

Adjusted estimates for differences between BMI categories in (A) ACR20, (B) ACR50 and (C) ACR70 response rates at month 6 and (D) rates of radiographic non-progression (change from baseline in mTSS ≤0.5) at month 24 (FAS, no imputation). Based on logistic regression model that includes the variables: age, gender, baseline BMI, baseline HAQ-DI score, race, smoking history, baseline glucocorticoid use, history of myocardial infarction, prior TNFi failure, seropositivity, baseline methotrexate use, baseline opioid use, baseline pain (VAS), baseline swollen joint count and baseline tender joint count. Red text indicates statistical significance for difference from BMI <25 kg/m² as 95% CI does not include 0. For this analysis, a difference from the baseline BMI <25 kg/m² category (reference) of ≥0.10 was considered clinically meaningful. ACR, American College of Rheumatology; BID, twice daily; BMI, body mass index; FAS, full analysis set; HAQ-DI, Health Assessment Questionnaire-Disability Index; mTSS, modified Total Sharp Score; TNFi, tumour necrosis factor inhibitors; VAS, Visual Analogue Scale.

Figure 2

Adjusted estimates for LS mean differences (ANCOVA) between BMI categories in change from baseline in (A) DAS28-4(ESR), (B) DAS28-4(CRP), (C) CDAI and (D) HAQ-DI at month 6 (FAS, no imputation). Based on ANCOVA model that includes the variables: age, gender, baseline BMI, baseline HAQ-DI score, baseline value of the response variable, race, smoking history, baseline glucocorticoid use, history of myocardial infarction, prior TNFi failure, seropositivity, baseline methotrexate use, baseline opioid use, baseline pain (VAS), baseline swollen joint count, and baseline tender joint count. Red text indicates statistical significance for difference from BMI <25 kg/m² as 95% CI does not include 0. For this analysis, a difference from the baseline BMI <25 kg/m² category (reference) of ≥1.2 (DAS28-4(ESR)), ≥1.0 (DAS28-4(CRP)), ≥12 (CDAI) and ≥0.22 (HAQ-DI) were considered clinically meaningful. Δ, change from baseline; ANCOVA, analysis of covariance; BID, twice daily; BMI, body mass index; CDAI, Clinical Disease Activity Index; DAS28-4(CRP), Disease Activity Score in 28 joints, C-reactive protein; DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; FAS, full analysis set; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least squares; MCID, minimum clinically important difference; TNFi, tumour necrosis factor inhibitors; VAS, Visual Analogue Scale.