University of Oulu

Williams, N. H., Jenkins, A., Goulden, N., Hoare, Z., Hughes, D. A., Wood, E., … Wilkinson, C. (2017). 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. Health Technology Assessment, 21(60), 1–180. https://doi.org/10.3310/hta21600

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

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Author: Williams, Nefyn H1,2; Jenkins, Alison1; Goulden, Nia1;
Organizations: 1School of Healthcare Sciences, Bangor University, Bangor, UK
2Betsi Cadwaladr University Health Board, Bangor, UK
3Research Institute of Primary Care and Health Sciences, Keele University, Keele, UK
4Arthritis Research UK Pain Centre Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK
5Centre for Primary Care and Public Health, Bart’s and the London School of Medicine and Dentistry, London, UK
6School of Healthcare Sciences, Cardiff University, Cardiff, UK
7 National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK
8Centre 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
9Medical Research Centre Oulu, University of Oulu, Oulu, Finland
10Rheumatology Department, Geneva University Hospitals, Geneva, Switzerland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 43.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019081223901
Language: English
Published: National Institute for Health Research, 2017
Publish Date: 2019-08-12
Description:

Abstract

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.

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.

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Series: Health technology assessment
ISSN: 1366-5278
ISSN-E: 2046-4924
ISSN-L: 1366-5278
Volume: 21
Issue: 60
Pages: 1 - 180
DOI: 10.3310/hta21600
OADOI: https://oadoi.org/10.3310/hta21600
Type of Publication: A1 Journal article – refereed
Field of Science: 3141 Health care science
Subjects:
Funding: Nefyn H Williams declares membership of the Health Technology Assessment (HTA) Primary Care, Community and Preventative Interventions Panel. Dyfrig A Hughes reports other grants from National Institute for Health Research (NIHR) during the conduct of the study and membership of the HTA Clinical Trials Board from 2010 to 2016, the HTA Funding Teleconference from 2015 to 2016 and the Pharmaceuticals Panel from 2008 to 2012. Eifiona Wood reports other grants from NIHR during the conduct of the study. Nadine E Foster declares membership of the HTA Primary Care, Community and Preventative Interventions Panel. David A Walsh reports grants from Pfizer Ltd and personal fees from Novartis Pharmaceuticals UK Ltd outside the submitted work. Kika Konstantinou reports other grants from NIHR during the conduct of the study. Jaro Karppinen reports personal fees from lectures (Pfizer Ltd, Merck & Co., Inc. and ORION Pharma GmbH), personal fees from a scientific advisory board (Axsome Therapeutics Inc.) and personal fees from stocks (ORION Pharma GmbH) outside the submitted work. Stephane Genevay reports grants from AbbVie Inc., Merck & Co., Inc., Pfizer Ltd, University Hospitals of Geneva, the Rheumasearch Foundation, Fondation de bienfaisance Eugenio Litta and Centre de Recherches outside the submitted work.
Copyright information: © Queen’s Printer and Controller of HMSO 2017. This work was produced by Williams et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.