Alternative tumour necrosis factor inhibitors (TNFi) or abatacept or rituximab following failure of initial TNFi in rheumatoid arthritis: the SWITCH RCT


Rheumatoid arthritis (RA) is a long-term problem that causes pain and swelling (inflammation) in the joints. The National Institute for Health and Care Excellence (NICE)’s guidance recommends commencement of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on diagnosis, usually methotrexate (MTX) and/or additional csDMARDs. If patients fail to respond to these and demonstrate high disease activity, NICE recommends the use of biologic disease-modifying antirheumatic drugs (bDMARDs). Four different classes of bDMARD are available. Tumour necrosis factor inhibitor (TNFi) is the most commonly used. However, up to 30–40% of patients fail to respond or lose an initial response to this bDMARD. In this setting, of the other three classes of bDMARD available, NICE recommends use of only rituximab, which not all patients respond to. This guidance thus limits the use of other potentially effective treatments (alternative TNFi, abatacept and tocilizumab) and is in the absence of any direct trial comparisons.

The aim of the SWITCH trial was to find out whether or not two alternative biologics (alternative TNFi or abatacept) were as good as rituximab at improving disease activity, quality of life, safety and cost-effectiveness in patients who did not respond to their initial TNFi treatment.

Between July 2012 and December 2014, 122 patients from 35 hospitals were recruited into the trial and randomly put into three treatment groups (1) rituximab, (2) alternative TNFi or (3) abatacept. The plan was to recruit 477 patients into the SWITCH trial. The trial was stopped early because of slow recruitment (largely attributable to operational challenges throughout the study period), achieving only 122 patients enrolled, and as a result was too small to test if either drug works as well as rituximab in reducing disease activity. A similar general improvement in patients’ physical functioning, quality of life relating to their RA, general health and safety over the 12-month period was apparent for all three treatments.

Switching to alternative TNFi may be cost-effective compared with the current treatment; however, the use of abatacept is unlikely to be cost-effective.

Alternative options to rituximab may work in patients who do not respond to their first biologic therapy, but uncertainty remains about which treatments to choose following an initial TNFi treatment failure.


The clinical question of whether or not alternative bDMARDs and rituximab are comparable in efficacy and safety outcomes in patients with RA who had not responded adequately to an initial TNFi bDMARD and MTX remains unresolved. The lack of evidence, which is based on a single treatment (rituximab) being appropriate for all patients, limits guidance options. Had the study been extended to enable recruitment to target, definitive evidence on whether or not either of the interventions were non-inferior to rituximab may have been provided, which may have opened up further treatment options for patients.


Publications and outputs

Coy NCN, Brown S, Bosworth A, Davies CT, Emery P, Everett CC, Fernandez C, Gray JC, Hartley S, Hulme C, Keenan AM, McCabe C, Redmond A, Reynolds C, Scott D, Sharples LD, Pavitt S, Buch MH. The 'Switch’ study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF inhibitor drug. BMC Musculoskelet Disord (2014) 15: 452; doi:10.1186/1471-2474-15-452.