The protocol of a clinical effectiveness trial comparing standard step-up care, early combination DMARD therapy and early use of TNF inhibitors for the treatment of moderate to severe psoriatic arthritis: the 3-arm parallel group SPEED randomized controlled trial

Marion Watson, William Tillett, Deepak Jadon, M Sofia Massa, Anne Francis, Nicola Gullick, Ines Rombach, Yvonne Sinomati, Laura Tucker, Laura C Coates

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: The aim of the Severe Psoriatic arthritis - Early intervEntion to control Disease trial is to compare outcomes in psoriatic arthritis (PsA) patients with poor prognostic factors treated with standard step-up conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), combination csDMARDs or a course of early biologics.

DESIGN: This multicentre UK trial was embedded within the MONITOR-PsA cohort, which uses a trial within cohort design.

METHODS AND ANALYSIS: Patients with newly diagnosed PsA and at least one poor prognostic factor (polyarthritis, C-reactive protein >5 mg/dL, health assessment questionnaire >1, radiographic erosions) were randomized equally and open-label to either standard care with 'step-up' csDMARD therapy, initial therapy with combination csDMARDs (methotrexate with either sulfasalazine or leflunomide) or to early biologics induction therapy (adalimumab plus methotrexate). The primary outcome is the PsA disease activity score at week 24.

ETHICS: Ethical approval for the study was granted by the South Central Research Ethics Committee (ref 18/SC/0107).

DISCUSSION: Treatment recommendations for PsA suggest more intensive therapy for those with poor prognostic factors but there are no studies that have previously used prognostic factors to guide therapy. Applying initial intensive therapy has shown improved outcomes in other inflammatory arthritides but has never been tried in PsA. Combination csDMARDs have shown some superiority over single therapies but there are limited data and concerns about side effects. Early use of biologics has also been shown to be superior to methotrexate but these drugs are costly and not usually funded first line. However, if a short course of biologics can rapidly suppress inflammation allowing treatment to be withdrawn and response maintained on methotrexate, this may be a cost-effective model for early use.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT03739853) and EudraCT (2017-004542-24).

Original languageEnglish
JournalTherapeutic Advances in Musculoskeletal Disease
Volume16
Early online date30 May 2024
DOIs
Publication statusE-pub ahead of print - 30 May 2024

Data Availability Statement

Availability of data and materials Data are available upon reasonable request. Participant-level dataset and statistical code will be made available upon reasonable request to the Oxford Clinical Trials Research Unit and the CI, once the study findings have been published in full. Some specific data items may not be shared to maintain participant anonymity

Acknowledgements

The SPEED study team acknowledges the expert statistical input of Associate Professor Susan Dutton in the development of the study proposal and the OCTRU programming team for support with the preparation and maintenance of the study database.

Keywords

  • biologics
  • clinical trial
  • polyarthritis
  • psoriatic arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Orthopedics and Sports Medicine

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