Title: SWITCH - Randomised- controlled trial of switching to alternative tumour necrosis factor-blocking drugs or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-blocking drug
Funder: Department of Health (England)

Abstract: DESIGN: First multi-centre randomised controlled open-label trial comparing alternative mechanism TNF-antagonist or abatacept with (NICE-approved) rituximab in patients who have failed an initial anti-TNF drug. There is currently little evidence on how best to utilise these biological therapies following first anti-TNF drug failure. While initial studies may have suggested value in switching from one TNF-blocking drug to another or switching to abatacept NICE has not approved these approaches in the absence of substantial evidence. The study will fill a significant unmet gap in our current knowledge-base and provide clear guidance to the clinician. SETTING: Hospital-based rheumatology out-patient departments throughout England. 16 centres (that constitute the largest centres using biological therapy) have agreed to participate via the Arthritis Research Campaigns Adult Inflammatory Arthritis Clinical Study Group. Based on each centres number of patients curently on a first anti-TNF and number of new patients usually starting a first anti-TNF per annum and a conservative estimation of non-response that has been reported a recruitment time of 30 months has been calculated. This has enabled us to draw up a strong recruitment strategy for SWITCH that is robust realistic and achievable and aimed to deliver the large number of RA patients (870) required to answer this challenging clinical problem. TARGET POPULATION: Men and women with rheumatoid arthritis (seropositive and seronegative types to rheumatoid factor /- cyclic citrullinated peptide antibody) who have failed a first TNF-blocking drug and have active RA (DAS28>5.1). All patients should be able to take methotrexate (MTX) to allow successful randomisation [as 2 of the therapies (infliximab and rituximab) requires MTX co-prescribing]. HEALTH TECHNOLOGIES ASSESSED: Patients will be allocated into three equal groups: i) alternative mechanism TNF-antagonist drug [TNF monoclonal antibody (infliximab or adalimumab) or TNF receptor fusion protein (etanercept)] ii) abatacept (T-cell costimulation blockade) or iii) rituximab (B-cell depletion). Allocation will be by a computer-generated minimisation programme stratified by centre disease duration (less than 5years and >/= 5 years) primary versus secondary non-response to initial TNF-antagonist and seropositive versus seronegative type. As rituximab is the only NICE recommended biologic therapy following TNF-antagonist failure and no direct comparison of abatacept and rituximab has been performed rituximab remains the comparison group; the study will compare Abatacept and TNF-blockade against rituximab but will not directly compare TNF-blockade and Abatacept. PRIMARY OUTCOME: Proportion of patients that achieve a reduction in disease activity score 28 (DAS28) of at least 1.2 at 6 months with no associated toxicity necessitating treatment withdrawal. SECONDARY OUTCOMES: i) DAS28 score reduction of >/= to 1.2 from baseline at months 3 9 and 12. Additionally at 369 and 12 months: ii) DAS28 low disease acitivity (<3.2) and remission (<2.6) rates iii)EULAR and ACR response scores iv)RA Quality of Life vi) Health assessment questionnaire-disability-index vii)Euro-Qol 5-dimension vi)Hospital anxiety and depression scale viii)SF-6 with health economic analysis ix)Change in plain x-ray score from baseline to month 12 x)Patient acceptability of treatment questionnaire.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM