Op0050 adalimumab Introduction Versus Methotrexate Dose Escalation in Patients With Inadequately Controlled Psoriatic Arthritis: Results From Randomized Phase 4 Control Study

Abstract

Background:Methotrexate (MTX) is often used as first-line therapy for patients (pts) with psoriatic arthritis (PsA) despite limited efficacy and data on appropriate dosage. Minimal Disease Activity (MDA) is suggested as an optimal treat-to-target outcome. Biologic disease-modifying antirheumatic drugs (bDMARDs) have demonstrated improved outcomes (including MDA rates) over MTX. However, more data are needed to define the optimal timing of bDMARD initiation and characterize efficacy of MTX dose escalation, to achieve optimal outcomes.Objectives:To compare achievement of MDA between adding adalimumab (ADA) vs escalating MTX dose in PsA pts with inadequate disease control after initial MTX therapy.Methods:The open-label, 2-part CONTROL study enrolled bDMARD-naive adult pts with active PsA (not in MDA at screening and ≥3 tender and ≥3 swollen joints) despite MTX 15 mg every wk (ew) for ≥4 wks. Pts were randomized to ADA 40 mg every other wk + MTX 15 mg (ADA+MTX) or escalated MTX to 20–25 mg ew or highest tolerable dose during 16-wk part 1 (Fig 1). The primary endpoint was achievement of MDA, defined as fulfilling ≥5 of the 7 criteria: tender joint count 68 (TJC68) ≤1, swollen joint count 66 (SJC66) ≤1, Psoriasis Area Severity Index (PASI) ≤1 or body surface area (BSA) ≤3%, pt’s pain (visual analogue scale [VAS] 0–100) ≤15, Pt’s Global Assessment of disease activity (PtGA) VAS ≤20, Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5 and tender entheseal points (0–8) ≤1. Key secondary efficacy endpoints were achievement of ACR20 and PASI75 and change from baseline in HAQ-DI and Leeds Enthesitis Index (LEI) at wk 16.Results:Overall, 246 pts were randomized; 245 received treatment (ADA+MTX, n=123; escalated MTX, n=122); 117 (95%) pts and 110 (90%) pts, respectively, completed part 1. Baseline characteristics were similar between groups (Table). During part 1, the average dose of MTX was 21.8 mg/wk (55% on oral MTX) in the escalated MTX group. Significantly higher proportion of pts in ADA+MTX (42%) vs escalated MTX (13%) group achieved MDA at wk 16 (non-responder imputation [NRI]; difference [95% CI] 28% [18%–39%];P<0.001;Fig 2). Observed case analysis confirmed the NRI analysis. Lower MDA rates at wk 16 were observed in the escalated MTX arm regardless of prior MTX duration (Fig 2). Significant improvements in key secondary endpoints were also observed with ADA+MTX vs escalated MTX (allP<0.05;Fig 2). In part 1, the proportion of patients with adverse events was similar between groups (ADA+MTX, 62% vs escalated MTX, 57%); no opportunistic infections, tuberculosis, malignancies, or deaths were reported during part 1.Conclusion:A significantly higher proportion of pts achieved MDA at wk 16 after introducing ADA compared with escalating MTX dose; higher rates were observed regardless of prior MTX duration. Significantly higher responses in musculoskeletal, skin, and quality of life measures were observed with ADA+MTX vs escalated MTX. No new safety signals with ADA were identified in this pt population.Table 1.Baseline DemographicsCharacteristics, mean (SD)ADA+MTXn=123Escalated MTXn=122Female, n (%)64 (52.0)59 (48.4)Age, y51.4 (12.2)48.8 (12.7)BSA >3%, n (%)74 (60.2)78 (63.9)Pt pain63.7 (19.5)62.3 (20.9)PtGA65.0 (19.9)62.9 (20.9)HAQ-DI1.2 (0.6)1.2 (0.7)LEI + plantar count3.5 (2.1)3.5 (2.1)Disclosure of Interests:Laura C Coates: None declared, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Liang Chen Shareholder of: AbbVie, Employee of: AbbVie, Mudra Kapoor Shareholder of: AbbVie, Employee of: AbbVie, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes

“…Seventeen trials were not included in the NMA either because they did not report results or did not report them at a time point of interest or because the dosing regimen during the randomised treatment phase was unclear. One further trial was considered for the NMA, but due to a lack of common comparator with other studies in the network it could not be included 35. Data from 46 unique RCTs were included in at least one NMA.…”

“…Patient eligibility criteria across the included studies were largely consistent. Thirty-eight trials required patients to have been diagnosed with PsA for a minimum of 3 months,17–20 22 23 26 36–65 and 36 trials used CASPAR as PsA diagnostic criteria 17–20 22 24 26 35 37–40 42 45–57 60–62 64 66–69. All trials except for GO-DACT64 and MAXIMISE69 reported the number of swollen and tender joints required at baseline.…”

“…More variable characteristics were the duration of PsA (ranging from 3.266 to 11.4 years),43 and the percentage of females (ranging from 37.1%63 and 64.6%22). The number of patients with prior exposure to biological therapies varied across trials from 100% exposure in three trials,47 54 57 to no exposure in twenty 18 35 41–46 49 53 59 62–66 69–72. Twenty further RCTs reported the percentage of patients previously exposed to biologics, ranging from 3.2%55 to 61.1% 24.…”

“…Twenty further RCTs reported the percentage of patients previously exposed to biologics, ranging from 3.2%55 to 61.1% 24. Ten trials included 100% of patients with prior exposure to csDMARDs 24 26 35 43 45 47 53 55 56 71. Twelve further RCTs reported the percentage of patients previously exposed to csDMARDs, ranging from 13.1%66 to 88.1% 19…”

Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis

“…The NMA included 26 RCTs (20,23,24,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49) that assessed the ACR 50 outcome at 6-month follow-up.…”