Severe Psoriatic Arthritis - Early intervEntion to Control Disease: the SPEED Trial

NCT03739853 | Completed Phase 4 Results DMC

• 1 other identifier: 18/SC/0107
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

SPEED is a three arm interventional trial nested within a cohort (Trials Within Cohorts or TWiCs design). This tests more aggressive early therapy in patients newly diagnosed with moderate to severe PsA. Arm 1 will receive standard step up therapy in the cohort and act as the control group. Arm 2 will receive early combination conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). Arm 3 will receive early tumour necrosis factor (TNF) inhibitor therapy.

Conditions

Psoriatic Arthritis

Outcome Measures

Primary Outcomes (1)

• Psoriatic Arthritis Disease Activity Score (PASDAS)

  A composite measure of PsA disease activity. This score is a composite measure of disease activity in PsA. There is only one total score which ranges from 0-10 with higher numbers indicating more active disease. Low disease activity is defined as \<3.2.

  24 weeks

Secondary Outcomes (3)

• Psoriatic Arthritis Disease Activity Score (PASDAS)

  48 weeks

• Minimal Disease Activity (MDA)

  12, 24, 36, 48 weeks

• Psoriatic Arthritis Impact of Disease (PsAID)

  12, 24, 36, 48 weeks

Study Arms (3)

Standard care

ACTIVE COMPARATOR

Control 'step-up' therapy in the cohort (MONITOR-PsA study). Therapy for the cohort is defined by standard NHS practice following international recommendations and National requirements for the prescription of biologic therapy\[19-22\]. Commonly Initial therapy will be with methotrexate alone (15mg/week rising to 25mg/week as tolerated by week 8 of therapy) unless this is contraindicated. In cases of non-response or intolerance to methotrexate, participants will have an alternative DMARD (most commonly sulfasalazine or leflunomide) added or switched to. In cases of failure of two DMARDs, treatment can be escalated to biologic therapy as per National Institute for Health and Clinical Excellence (NICE) recommendations. If the requisite disease activity is not met or if there are contraindications to biologics, alternative DMARD combinations will be used.

Drug: Methotrexate; Drug: Sulfasalazine; Drug: Leflunomide

Combination csDMARD

EXPERIMENTAL

Arm 2 - Combination DMARD arm. All participants will be prescribed methotrexate with an additional DMARD (either sulfasalazine or leflunomide) at baseline. Response will be assessed after 12 weeks of therapy using the Minimal Disease Activity (MDA) criteria. Participants who achieve the MDA criteria by week 12 on this combination therapy will continue . Participants who show a significant response by in week 12 (a reduction in tender and swollen joint counts of at least 20%) but do not yet meet the MDA criteria should continue on this therapy for an additional 12 weeks before review. Participants failing to show significant response (reduction in joint counts by less than 20%) by week 12 on this combination therapy or those failing to meet MDA criteria by week 24 will be eligible for rescue therapy

Drug: Methotrexate; Drug: Sulfasalazine; Drug: Leflunomide

Early TNF inhibition

EXPERIMENTAL

Early biologic arm. All participants will be prescribed methotrexate (given weekly) with a TNF inhibitor (adalimumab given every two weeks) at baseline. Treatment with TNF inhibitor will be continued until week 24 at which time the TNF inhibitor will be tapered to week 32. The TNF inhibitor will be stopped completely after week 32 and participants will continue on methotrexate. In case of flare of disease, participants will be eligible for rescue therapy

Drug: Methotrexate; Drug: Adalimumab

Interventions

Methotrexate DRUG

Used in all three arms of study

Combination csDMARD; Early TNF inhibition; Standard care

Sulfasalazine DRUG

Used in arm 2 of study

Combination csDMARD; Standard care

Leflunomide DRUG

Used in arm 2 of study

Combination csDMARD; Standard care

Adalimumab DRUG

Used in arm 3 of the study only

Early TNF inhibition

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give informed consent for participation in the trial.
• Male or Female, aged 18 years or above.
• Participants consented to the PsA inception cohort (MONITOR-PsA) and to be approached for alternate interventional therapies.
• Poor prognostic factors at baseline. Either
• Polyarticular disease with ≥5 active joints at baseline assessment OR
• Oligoarticular disease with \<5 active joints at baseline but with one or more of the following poor prognostic factors: raised C reactive protein, radiographic damage, health assessment questionnaire\>1
• Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter (or 2 years if received leflunomide unless treated with washout therapy) as in standard practice.
• Participant has clinically acceptable laboratory results within 28 days of baseline:
• Haemoglobin count \> 8.5 g/dL
• White blood count (WBC) \> 3.5 x 109/L
• Absolute neutrophil count (ANC) \> 1.5 x 109/L
• Platelet count \> 100 x 109/L
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase levels \<3 x upper limit of normal
• In the Investigator's opinion, is able and willing to comply with all trial requirements.
• Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the trial.

You may not qualify if:

• Previous treatment for articular disease with DMARDs including, but not limited to, methotrexate, sulfasalazine, leflunomide and ciclosporin
• Female patient who is pregnant, breast-feeding or planning pregnancy during the course of the trial.
• Significant renal (estimated glomerular filtration rate \<30ml/min) or hepatic impairment.
• Patients who test positive for Hepatitis B, C or HIV.
• Contraindication to any of the investigative drugs.
• Patients who currently abuse drugs or alcohol
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Patient with life expectancy of less than 6 months.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put patients at risk because of participation in the trial, or may influence the result of the trial, or their ability to participate in the trial.
• Participation in another research trial involving an investigational product in the past 12 weeks.
• Active tuberculosis (TB), chronic viral infections, recent serious bacterial infections, those receiving live vaccinations within 3 months of the anticipated first dose of study medication, or those with chronic illnesses that would, in the opinion of the investigator, put the participant at risk.
• Latent TB unless they have received appropriate anti-tuberculous treatment as per local guidelines
• History of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Oxford University Hospitals NHS Trust

Oxford, Oxfordshire, OX3 7LD, United Kingdom

Location

Related Publications (1)

• Watson M, Tillett W, Jadon D, Massa MS, Francis A, Gullick N, Rombach I, Sinomati Y, Tucker L, Coates LC. 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. Ther Adv Musculoskelet Dis. 2024 May 30;16:1759720X241240913. doi: 10.1177/1759720X241240913. eCollection 2024.

  PMID: 38826570 DERIVED

MeSH Terms

Conditions

Arthritis, Psoriatic

Interventions

Methotrexate; Sulfasalazine; Leflunomide; Adalimumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Some missing data in primary and secondary outcomes due to COVID and other missed visits

Results Point of Contact

• Title: Laura Coates
• Organization: University of Oxford, NDORMS

laura.coates@ndorms.ox.ac.uk

+441865737838

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded assessor will perform clinical evaluations.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 14, 2018
• Study Start: May 14, 2019
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: November 26, 2025
• Results First Posted: November 26, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)