SPEED

What is psoriatic arthritis?
Psoriatic arthritis (PsA) is a type of arthritis that can affect people who have psoriasis. It causes painful, swollen joints and can make everyday activities harder. Some people have a more severe form of PsA, especially if they have many swollen joints, high levels of inflammation in blood tests, or early signs of joint damage. These are called poor prognostic factors, meaning the disease is more likely to get worse.

What was this study trying to find out?
Doctors usually start treatment with one medicine and increase it slowly if needed (“step-up care”). But for people with more severe PsA, guidelines suggest using stronger treatment earlier—although until now, this advice was not supported by clear evidence.

The SPEED study wanted to find out whether starting stronger treatment earlier helps people with severe PsA get better faster, compared with standard step-up care.

Summary

Treatment recommendations for psoriatic arthritis (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 disease-modifying anti-rheumatic drugs (DMARDs) 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  However, if a short course of biologics can rapidly suppress inflammation allowing treatment to be withdrawn and response maintained on methotrexate, this may be a cost-effective model for early use.  The aim of the SPEED trial is to compare outcomes in PsA patients with poor prognostic factors treated with standard step-up DMARDs, combination DMARDs or a course of early biologics.

Background

In psoriatic arthritis (PsA), EULAR treatment recommendations advise a treat-to-target  approach with a more intensive therapy for those with poor prognostic factors but there is no evidence for this to date, meaning doctors do not know the best treatment to give these patients. We aimed to compare the efficacy and safety of intensive treatment strategies in patients with poor prognosis PsA.

Aims and objectives

Our primary objective is to compare the initial effectiveness of early combination DMARD therapy (arm 2) and early use of TNF inhibitors (arm 3) with standard step up care (received in the TWiCs cohort, arm 1) using the PsA disease activity score (PASDAS) score (on a continuous scale) at 24 weeks.

Our secondary objectives will explore the speed of response using PASDAS and time to achieve minimal disease activity (MDA) criteria, longer term response at 48 weeks and impact on quality of life. Cost effectiveness of the different treatment arms will also be compared with prospectively collected health economics data.

Our exploratory objectives include domain specific responses (e.g. reduction in skin psoriasis, enthesitis, dactylitis), quality of life, treatment satisfaction, safety and radiographic change.

Study design

The SPEED study is an open-label randomised controlled trial of adults with moderate-severe PsA nested within a cohort using a trials within cohorts or TWiCs design. The trial recruited at 11 sites across the UK within the MONITOR-PsA cohort. Participants in the MONITOR-PsA cohort may be offered interventional trials with other members of the cohort acting as comparative controls where they have consented to this.  In the SPEED trial, participants in the cohort with moderate-severe diseases are randomised 1:1:1 to standard step-up care, combination csDMARDs or early biologics, with a primary outcome being the PASDAS score after 24 weeks on therapy.