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.
- Williams NH School of Healthcare Sciences, Bangor University, Bangor, UK.
- Jenkins A School of Healthcare Sciences, Bangor University, Bangor, UK.
- Goulden N School of Healthcare Sciences, Bangor University, Bangor, UK.
- Hoare Z School of Healthcare Sciences, Bangor University, Bangor, UK.
- Hughes DA School of Healthcare Sciences, Bangor University, Bangor, UK.
- Wood E School of Healthcare Sciences, Bangor University, Bangor, UK.
- Foster NE Research Institute of Primary Care and Health Sciences, Keele University, Keele, UK.
- Walsh DA Arthritis Research UK Pain Centre Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK.
- Carnes D Centre for Primary Care and Public Health, Bart's and the London School of Medicine and Dentistry, London, UK.
- Sparkes V School of Healthcare Sciences, Cardiff University, Cardiff, UK.
- Hay EM Research Institute of Primary Care and Health Sciences, Keele University, Keele, UK.
- Isaacs J National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK.
- Konstantinou K Research Institute of Primary Care and Health Sciences, Keele University, Keele, UK.
- Morrissey D Centre for Sports and Exercise Medicine, William Harvey Research Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- Karppinen J Medical Research Centre Oulu, University of Oulu, Oulu, Finland.
- Genevay S Rheumatology Department, Geneva University Hospitals, Geneva, Switzerland.
- Wilkinson C School of Healthcare Sciences, Bangor University, Bangor, UK.
- 2017-10-25
Published in:
- Health technology assessment (Winchester, England). - 2017
Adalimumab
Anti-Inflammatory Agents
Cost-Benefit Analysis
Humans
Injections, Subcutaneous
Patient Selection
Physical Therapy Modalities
Pilot Projects
Sciatica
Treatment Outcome
English
BACKGROUND
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.
OBJECTIVES
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.
DESIGN
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.
SETTING
Participants were referred from primary care and musculoskeletal services to outpatient physiotherapy clinics.
PARTICIPANTS
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.
INTERVENTIONS
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.
MAIN OUTCOME MEASURES
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.
SAMPLE SIZE
To detect an effect size of 0.4 with 90% power, a 5% significance level for a two-tailed t-test and 80% retention rate, 332 participants would have needed to be recruited.
ANALYSIS PLAN
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.
RESULTS
The internal pilot study was discontinued as a result of low recruitment after eight participants were recruited from two out of six sites. One site withdrew from the study before recruitment started, one site did not complete contract negotiations and two sites signed contracts shortly before trial closure. In the two sites that did recruit participants, recruitment was slow. This was partly because of operational issues, but also because of a low rate of uptake from potential participants.
LIMITATIONS
Although large numbers of invitations were sent to potential participants, identified by retrospective searches of general practitioner (GP) records, there was a low rate of uptake. Two sites planned to recruit participants during GP consultations but opened too late to recruit any participants.
CONCLUSION
The main failure was attributable to problems with contracts. Because of this we were not able to complete the internal pilot or to test all of the different methods for primary care recruitment we had planned. A trial of biological therapy in patients with sciatica still needs to be done, but would require a clearer contracting process, qualitative research to ensure that patients would be willing to participate, and simpler recruitment methods.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN14569274.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 60. See the NIHR Journals Library website for further project information.
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.
OBJECTIVES
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.
DESIGN
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.
SETTING
Participants were referred from primary care and musculoskeletal services to outpatient physiotherapy clinics.
PARTICIPANTS
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.
INTERVENTIONS
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.
MAIN OUTCOME MEASURES
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.
SAMPLE SIZE
To detect an effect size of 0.4 with 90% power, a 5% significance level for a two-tailed t-test and 80% retention rate, 332 participants would have needed to be recruited.
ANALYSIS PLAN
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.
RESULTS
The internal pilot study was discontinued as a result of low recruitment after eight participants were recruited from two out of six sites. One site withdrew from the study before recruitment started, one site did not complete contract negotiations and two sites signed contracts shortly before trial closure. In the two sites that did recruit participants, recruitment was slow. This was partly because of operational issues, but also because of a low rate of uptake from potential participants.
LIMITATIONS
Although large numbers of invitations were sent to potential participants, identified by retrospective searches of general practitioner (GP) records, there was a low rate of uptake. Two sites planned to recruit participants during GP consultations but opened too late to recruit any participants.
CONCLUSION
The main failure was attributable to problems with contracts. Because of this we were not able to complete the internal pilot or to test all of the different methods for primary care recruitment we had planned. A trial of biological therapy in patients with sciatica still needs to be done, but would require a clearer contracting process, qualitative research to ensure that patients would be willing to participate, and simpler recruitment methods.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN14569274.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 60. See the NIHR Journals Library website for further project information.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.3310/hta21600
- PMID 29063827
- Persistent URL
- https://folia.unifr.ch/global/documents/23353
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