Comparison between adalimumab introduction and methotrexate dose escalation in patients with inadequately controlled psoriatic arthritis (CONTROL): a randomised, open-label, two-part, phase 4 study

Laura C. Coates, William Tillett, Maria Antonietta D'Agostino, Proton Rahman, Frank Behrens, Erin L. McDearmon-Blondell, Xianwei Bu, Liang Chen, Mudra Kapoor, Philip G. Conaghan, Philip Mease

Research output: Contribution to journalArticlepeer-review

9 Citations (SciVal)

Abstract

Background: Many patients with psoriatic arthritis do not reach minimal disease activity (MDA) on methotrexate alone. This phase 4 open-label study aimed to compare attainment of MDA following introduction of adalimumab with methotrexate escalation in patients with psoriatic arthritis who do not reach MDA after an initial methotrexate course (≤15 mg every week). Methods: CONTROL was a phase 4, randomised, two-part, open-label study conducted in 14 countries and 46 sites. We recruited patients with confirmed active psoriatic arthritis, naive to biologic disease-modifying antirheumatic drugs, with an inadequate response to 15 mg or less of methotrexate. In part 1, patients were randomly assigned (1:1) to receive either methotrexate 15 mg (oral or subcutaneous) every week with the addition of adalimumab 40 mg (subcutaneously) every other week (adalimumab plus methotrexate group) or methotrexate (oral or subcutaneous) escalation up to 25 mg every week (escalated methotrexate group). Randomisation was done using Interactive Response Technology and stratified by the duration of methotrexate treatment (≤3 months and >3 months). In this open-label study there was no masking; participants, people giving the interventions, those assessing outcomes, and those analysing the data were aware of group assignment. The primary endpoint was the proportion of patients who reached MDA at 16 weeks. After 16 weeks (part 2), patients who reached MDA (responders) had their current therapy maintained or modified, wheras patients who did not reach MDA (non-responders) had their therapy escalated until 32 weeks. The primary endpoint in part 2 was the proportion of patients who reached MDA at 32 weeks, analysed in all patients who received one or more doses of study drug. The study is registered with ClinicalTrials.gov, NCT02814175. Findings: Between Aug 5, 2016, and March 19, 2020, 245 of 287 patients initially assessed were enrolled in the study (50% men and 50% women; 92% of patients were White). 123 patients were randomly assigned to receive adalimumab plus methotrexate and 122 patients to receive escalated methotrexate. All 245 patients were included in the primary analysis, and 227 completed part 1 and entered part 2. A significantly higher proportion of patients reached MDA at 16 weeks in the adalimumab plus methotrexate group (51 [41%] patients) compared with the escalated methotrexate group (16 [13%] patients; p<0·0001). Efficacy was generally maintained through 32 weeks for patients who reached MDA at 16 weeks, with 41 (80%) of 51 adalimumab responders and ten (67%) of 15 methotrexate responders maintaining MDA at 32 weeks. Of adalimumab non-responders, 17 (30%) of 57 patients reached MDA at 32 weeks after adalimumab escalation to every week dosing. Among methotrexate non-responders, 50 (55%) of 91 reached MDA after adalimumab introduction. In part 1, two patients in the adalimumab plus methotrexate group reported serious adverse events; and in part 2, one adalimumab responder, three adalimumab non-responders, and three methotrexate non-responders reported serious adverse events. No new safety signals were identified. Interpretation: Results from this novel treatment-strategy trial support the addition of adalimumab over escalating methotrexate in patients with psoriatic arthritis not reaching MDA after an initial methotrexate course. Safety results were consistent with the therapies' known safety profiles. Funding: AbbVie.

Original languageEnglish
Pages (from-to)e262-e273
JournalThe Lancet Rheumatology
Volume4
Issue number4
Early online date25 Feb 2022
DOIs
Publication statusPublished - 30 Apr 2022

Bibliographical note

Funding Information:
The study was funded by AbbVie. Medical writing support was provided by Jamie Urbanik, PharmD, Nancy Dudek (both of AbbVie), and Laura Chalmers, PhD (2 the Nth, Cheshire, UK), funded by AbbVie. PGC is supported in part through the NIHR Leeds Biomedical Research Centre; the views expressed in this manuscript are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. AbbVie and the authors thank Maja Hojnik, a former employee of AbbVie, Erica Cummings, and Aurore Diamand, from the AbbVie Clinical Operations Group, for contributions to the study conception and design. The authors also thank Jenny M Chan, Nael Mostafa, and Christine M Lee, all of AbbVie, for their support with the pharmacokinetic analyses.

Funding Information:
The study was funded by AbbVie. Medical writing support was provided by Jamie Urbanik, PharmD, Nancy Dudek (both of AbbVie), and Laura Chalmers, PhD (2 the Nth, Cheshire, UK), funded by AbbVie. PGC is supported in part through the NIHR Leeds Biomedical Research Centre; the views expressed in this manuscript are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. AbbVie and the authors thank Maja Hojnik, a former employee of AbbVie, Erica Cummings, and Aurore Diamand, from the AbbVie Clinical Operations Group, for contributions to the study conception and design. The authors also thank Jenny M Chan, Nael Mostafa, and Christine M Lee, all of AbbVie, for their support with the pharmacokinetic analyses.

Publisher Copyright:
© 2022 Elsevier Ltd

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Comparison between adalimumab introduction and methotrexate dose escalation in patients with inadequately controlled psoriatic arthritis (CONTROL): a randomised, open-label, two-part, phase 4 study'. Together they form a unique fingerprint.

Cite this