Subcutaneous Injection of Adalimumab Trial compared with Control (SCIATiC): a randomised controlled trial of adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica

Biological treatments such as adalimumab (Humira ; AbbVie Ltd, Maidenhead, UK) are antibodies targeting tumour necrosis factor alpha, released from ruptured intervertebral discs, which might be useful in sciatica. Recent systematic reviews concluded that they might be effective, but that a definitive randomised controlled trial was needed. Usual care in the NHS typically includes a physiotherapy intervention. To test whether or not injections of adalimumab plus physiotherapy are more clinically effective and cost-effective than injections of saline plus physiotherapy for patients with sciatica. Pragmatic, parallel-group, randomised controlled trial with blinded participants and clinicians, and an outcome assessment and statistical analysis with concurrent economic evaluation and internal pilot. Participants were referred from primary care and musculoskeletal services to outpatient physiotherapy clinics. Adults with persistent symptoms of sciatica of 1-6 months' duration and with moderate to high levels of disability. Eligibility was assessed by research physiotherapists according to clinical criteria for diagnosing sciatica. After a second eligibility check, trial participants were randomised to receive two doses of adalimumab (80 mg and then 40 mg 2 weeks later) or saline injections. Both groups were referred for a course of physiotherapy. Outcomes were measured at the start, and after 6 weeks' and 6 months' follow-up. The main outcome measure was the Oswestry Disability Index (ODI). Other outcomes: leg pain version of the Roland-Morris Disability Questionnaire, Sciatica Bothersomeness Index, EuroQol-5 Dimensions, 5-level version, Hospital Anxiety and Depression Scale, resource use, risk of persistent disabling pain, pain trajectory based on a single question, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia and adverse effects. To detect an effect size of 0.4 with 90% power, a 5% significance level for a two-tailed -test and 80% retention rate, 332 participants would have needed to be recruited. The primary effectiveness analysis would have been linear mixed models for repeated measures to measure the effects of time and group allocation. An internal pilot study would have involved the first 50 participants recruited across all centres. The primary economic analysis would have been a cost-utility analysis. The internal pilot study was discontinued as a result of low recruitment after eight participants were recruited from two out of six sit