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Body Mass Index and Treatment Response to Subcutaneous Abatacept in Patients with Psoriatic Arthritis: a Post Hoc Analysis of a Phase III Trial

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Body Mass Index and Treatment Response to Subcutaneous Abatacept in Patients with Psoriatic Arthritis: a Post Hoc Analysis of a Phase III Trial Psoriatic arthritis RMD Open: first published as 10.1136/rmdopen-2019-000934 on 30 May 2019. Downloaded from ORIGINAL ARTICLE Body mass index and treatment response to subcutaneous abatacept in patients with psoriatic arthritis: a post hoc analysis of a phase III trial Iain B McInnes, 1 Gianfranco Ferraccioli, 2 Maria-Antonietta D'Agostino, 3 Manuela Le Bars,4 Subhashis Banerjee,5 Harris A Ahmad,5 Yedid Elbez,6 Philip J Mease 7 To cite: McInnes IB, ABSTRACT Key messages Ferraccioli G, D'Agostino M-A, Objective This post hoc analysis of the phase III et al. Body mass index Active PSoriaTic Arthritis RAndomizEd TriAl (ASTRAEA) and treatment response to evaluated the effect of baseline body mass index (BMI) on What is already known about this subject? subcutaneous abatacept subsequent response to subcutaneous (SC) abatacept in ► Patients with psoriatic arthritis (PsA) tend to have in patients with psoriatic a higher body mass index (BMI) than the general arthritis: a post hoc analysis patients with psoriatic arthritis (PsA). Methods In ASTRAEA, patients with active PsA were population. A high BMI can be associated with less of a phase III trial. RMD Open favourable clinical outcomes with biologics, such as 2019;5:e000934. doi:10.1136/ randomised (1:1) to receive blinded weekly SC abatacept tumour necrosis factor inhibitors. rmdopen-2019-000934 125 mg or placebo for 24 weeks. Treatment response at week 24 was assessed by the proportions of patients What does this study add? copyright. achieving American College of Rheumatology 20% ► This analysis evaluated the relationship between Received 22 February 2019 improvement response, Disease Activity Score in 28 joints Revised 30 April 2019 BMI and treatment response to subcutaneous (SC) (DAS28 (C reactive protein (CRP))) ≤3.6 and <2.6, Health abatacept in patients with PsA. Accepted 3 May 2019 Assessment Questionnaire-Disability Index reduction ► Obese and overweight patients with PsA had a sta- http://rmdopen.bmj.com/ from baseline ≥0.35 and radiographic non-progression tistically similar treatment response to SC abatacept (defined as change from baseline ≤0 in PsA-modified total compared with patients who were underweight or Sharp/van der Heijde score). Responses were stratified by had normal BMI. baseline BMI (underweight/normal, <25 kg/m2; overweight, 25–30 kg/m2; obese, >30 kg/m2) and compared in How might this impact on clinical practice or univariate and multivariate models. future developments? Results Of 212/213 and 210/211 patients with ► These findings suggest that SC abatacept could be baseline BMI data in the abatacept and placebo groups, considered for patients with PsA irrespective of BMI respectively, 15% and 19% were underweight/normal, status. 36% and 27% were overweight, and 49% and 54% were on November 19, 2019 at University of Glasgow. Protected by obese. After adjusting for baseline characteristics, there were no significant differences for any outcome measure at week 24 with abatacept in the overweight or obese necrosis factor inhibitors (TNFis), a class of versus underweight/normal subgroup. In the placebo biologic (b) disease-modifying antirheumatic group, patients in the obese versus underweight/normal drugs (DMARDs), are an effective treatment subgroup were significantly less likely to achieve DAS28 (CRP) <2.6 at week 24 (OR 0.26; 95% CI 0.08 to 0.87; option for PsA; however, a meta-analysis of 20 p=0.03). randomised clinical trials and 34 observational Conclusion BMI does not impact clinical or radiographic studies in patients with rheumatic diseases, response to SC abatacept in patients with PsA. including PsA, concluded that obesity is associ- © Author(s) (or their Trial registration number NCT01860976. employer(s)) 2019. Re-use ated with reduced treatment response to TNFis permitted under CC BY-NC. No in these patients.2 The effect of obesity on the commercial re-use. See rights and permissions. Published efficacy of bDMARDs with other mechanisms by BMJ. INTRODUCTION of action is unclear. An understanding of the For numbered affiliations see Patients with psoriatic arthritis (PsA) are potential impact of BMI on treatment-related end of article. twice as likely as the general population to be outcomes in PsA is important for informing clinical decision-making in practice; therefore, Correspondence to obese, as defined by body mass index (BMI) 2 Iain B McInnes; ≥30 kg/m , with a prevalence of obesity information on the effect of obesity on the effi- iain. mcinnes@ glasgow. ac. uk among patients with PsA of 37%.1 Tumour cacy of non-TNFi bDMARDs for PsA is needed. McInnes IB, et al. RMD Open 2019;5:e000934. doi:10.1136/rmdopen-2019-000934 1 RMD Open RMD Open: first published as 10.1136/rmdopen-2019-000934 on 30 May 2019. Downloaded from Abatacept is a cytotoxic T lymphocyte-associated anti- baseline ≥0.35). Structural damage was assessed by deter- gen-4-immunoglobulin fusion molecule that selectively mining the rates of radiographic non-progression (defined modulates T-cell co-stimulation and activation through the as change from baseline ≤0 in PsA-modified total Sharp/ inhibition of the CD80/CD86:CD28 co-stimulatory signal. van der Heijde score). T-cell-driven pathways are implicated in the pathogenesis of immunological diseases including PsA, making abatacept a Statistical analyses plausible therapeutic candidate.3 Indeed, abatacept, avail- Baseline patient demographics and disease characteris- able as an intravenous or subcutaneous (SC) formulation, tics were analysed descriptively according to the baseline is approved for the treatment of moderate-to-severe rheu- BMI subgroup (percentage for categorical variables and matoid arthritis (RA), juvenile idiopathic arthritis and PsA.4 mean (SD) for continuous variables). Rates for treatment Evidence from interventional trials and real-world studies response and radiographic non-progression in each BMI has shown that BMI does not affect treatment response to subgroup were determined at week 24 and compared abatacept in patients with RA.5 6 However, there are limited between subgroups using univariable and multivariable data on the impact of BMI on response to abatacept in analyses with the underweight/normal BMI subgroup patients with PsA. as the reference. Key potential confounding factors for In the randomised, double-blind, placebo-controlled, treatment efficacy were included in the multivariable international phase III Active PSoriaTic Arthritis RAndom- model. Results are presented as ORs with corresponding izEd TriAl (ASTRAEA), the American College of Rheu- 95% CIs; p values were calculated for each treatment matology 20% improvement (ACR20) response rate in outcome by BMI subgroup, based on a logistic regression patients with PsA at week 24 was significantly higher with model. The ORs were statistically significant when the abatacept versus placebo.7 Here, we present findings from 95% CIs did not cross 1. An additional stratified multi- an analysis of ASTRAEA to explore the impact of patient variable analysis was performed to evaluate treatment BMI at baseline on the response to SC abatacept. responses by baseline BMI subgroup at week 24, (i) in patients who received abatacept without any concomitant METHODS non-bDMARD (defined as not receiving any of actarit, Study design and treatment apremilast, auranofin, aurothioglucose, aurotioprol, A post hoc analysis of the ASTRAEA study was conducted aurotioprol gold salt, azathioprine, bucillamine, chloram- to evaluate the effect of baseline BMI on the response bucil, chloroquine, cyclosporine, gold salts, gold sodium copyright. to SC abatacept in patients with PsA. The study design, thiomalate, hydroxychloroquine, leflunomide, loben- ethics approvals, study population, patient eligibility zarit, methotrexate, mizoribine, penicillamine, sulfasala- zine, tiopronin or tofacitinib); concomitant NSAIDs, oral criteria and main endpoints of ASTRAEA have been http://rmdopen.bmj.com/ reported previously.7 The trial is registered at www. clin- corticosteroids or topical corticosteroids were permitted, icaltrials. gov. and (ii) in those who received abatacept in combination Briefly, patients with active PsA and an inadequate with a non-bDMARD. response or intolerance to ≥1 non-bDMARD were randomised (1:1) to receive blinded weekly SC abatacept RESULTS 125 mg or placebo for 24 weeks. Concomitant treatment Analysis population with methotrexate, leflunomide, sulfasalazine or hydroxy- Baseline BMI data were available for 212/213 and 210/211 chloroquine; non-steroidal anti-inflammatory drugs patients randomised to abatacept or placebo, respectively. on November 19, 2019 at University of Glasgow. Protected by (NSAIDs) and oral corticosteroids (<10 mg/day); and use In the abatacept group, 31/212 (14.6%) patients were of low-potency topical corticosteroids in sensitive areas underweight/normal, 77/212 (36.3%) patients were were permitted. Patients without ≥20% improvement overweight and 104/212 (49.1%) patients were obese. In from baseline in swollen or tender joint counts at week the placebo group, 39/210 (18.6%) patients were under- 16 were switched to open-label abatacept (early escape) weight/normal, 57/210 (27.1%) were overweight and for 28 weeks. Patients designated as an early escape or 114/210 (54.3%) were obese. Patient demographic and with missing data were imputed as non-responders. disease characteristics at baseline by BMI subgroup are presented in table 1. Study assessments For patients with available baseline BMI data, all analyses Treatment response by BMI—univariate
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