Anti-TNF (adalimumab) Injection for the Treatment of Pain-predominant Early-stage Frozen Shoulder: the Anti-Freaze-Feasibility Randomised Controlled Trial

Overview

Journal BMJ Open

Specialty General Medicine

Date 2024 May 1

PMID 38692727

Authors

Sally Hopewell

Cynthia Srikesavan

Alison Evans

Fema Er

Amar Rangan

Jane Preece

Anne Francis

M Sofia Massa

Marc Feldmann

Sarah Lamb

Jagdeep Nanchahal

Affiliations

Soon will be listed here.

Abstract

Objective: The Anti-Freaze-F (AFF) trial assessed the feasibility of conducting a definitive trial to determine whether intra-articular injection of adalimumab can reduce pain and improve function in people with pain-predominant early-stage frozen shoulder.

Design: Multicentre, randomised feasibility trial, with embedded qualitative study.

Setting: Four UK National Health Service (NHS) musculoskeletal and related physiotherapy services.

Participants: Adults ≥18 years with new episode of shoulder pain attributable to early-stage frozen shoulder.

Interventions: Participants were randomised (centralised computer generated 1:1 allocation) to either ultrasound-guided intra-articular injection of: (1) adalimumab (160 mg) or (2) placebo (saline (0.9% sodium chloride)). Participants and outcome assessors were blinded to treatment allocation. Second injection of allocated treatment (adalimumab 80 mg) or equivalent placebo was administered 2-3 weeks later. PRIMARY FEASIBILITY OBJECTIVES: (1) Ability to screen and identify participants; (2) willingness of eligible participants to consent and be randomised; (3) practicalities of delivering the intervention; (4) SD of the Shoulder Pain and Disability Index (SPADI) score and attrition rate at 3 months.

Results: Between 31 May 2022 and 7 February 2023, 156 patients were screened of whom 39 (25%) were eligible. The main reasons for ineligibility were other shoulder disorder (38.5%; n=45/117) or no longer in pain-predominant frozen shoulder (33.3%; n=39/117). Of the 39 eligible patients, nine (23.1%) consented to be randomised (adalimumab n=4; placebo n=5). The main reason patients declined was because they preferred receiving steroid injection (n=13). All participants received treatment as allocated. The mean time from randomisation to first injection was 12.3 (adalimumab) and 7.2 days (placebo). Completion rates for patient-reported and clinician-assessed outcomes were 100%.

Conclusion: This study demonstrated that current NHS musculoskeletal physiotherapy settings yielded only small numbers of participants, too few to make a trial viable. This was because many patients had passed the early stage of frozen shoulder or had already formulated a preference for treatment.

Trial Registration Number: ISRCTN 27075727, EudraCT 2021-03509-23, ClinicalTrials.gov NCT05299242 (REC 21/NE/0214).

References

Bunker T, ANTHONY P . The pathology of frozen shoulder. A Dupuytren-like disease. J Bone Joint Surg Br. 1995; 77(5):677-83. View

Page M, Green S, Kramer S, Johnston R, McBain B, Buchbinder R . Electrotherapy modalities for adhesive capsulitis (frozen shoulder). Cochrane Database Syst Rev. 2014; (10):CD011324. PMC: 10898218. DOI: 10.1002/14651858.CD011324. View

Nicholas M, McGuire B, Asghari A . A 2-item short form of the Pain Self-efficacy Questionnaire: development and psychometric evaluation of PSEQ-2. J Pain. 2014; 16(2):153-63. DOI: 10.1016/j.jpain.2014.11.002. View

Hanchard N, Goodchild L, Thompson J, OBrien T, Davison D, Richardson C . Evidence-based clinical guidelines for the diagnosis, assessment and physiotherapy management of contracted (frozen) shoulder: quick reference summary. Physiotherapy. 2012; 98(2):117-20. DOI: 10.1016/j.physio.2012.01.001. View

Smith S, Devaraj V, Bunker T . The association between frozen shoulder and Dupuytren's disease. J Shoulder Elbow Surg. 2001; 10(2):149-51. DOI: 10.1067/mse.2001.112883. View

Hand G, Athanasou N, Matthews T, Carr A . The pathology of frozen shoulder. J Bone Joint Surg Br. 2007; 89(7):928-32. DOI: 10.1302/0301-620X.89B7.19097. View

Page M, Green S, Kramer S, Johnston R, McBain B, Chau M . Manual therapy and exercise for adhesive capsulitis (frozen shoulder). Cochrane Database Syst Rev. 2014; (8):CD011275. PMC: 10882424. DOI: 10.1002/14651858.CD011275. View

Wang W, Shi M, Zhou C, Shi Z, Cai X, Lin T . Effectiveness of corticosteroid injections in adhesive capsulitis of shoulder: A meta-analysis. Medicine (Baltimore). 2017; 96(28):e7529. PMC: 5515778. DOI: 10.1097/MD.0000000000007529. View

Mintken P, Cleland J, Whitman J, George S . Psychometric properties of the Fear-Avoidance Beliefs Questionnaire and Tampa Scale of Kinesiophobia in patients with shoulder pain. Arch Phys Med Rehabil. 2010; 91(7):1128-36. DOI: 10.1016/j.apmr.2010.04.009. View

10.

Larsen S, Krogsgaard D, Aagaard Larsen L, Iachina M, Skytthe A, Frederiksen H . Genetic and environmental influences in Dupuytren's disease: a study of 30,330 Danish twin pairs. J Hand Surg Eur Vol. 2014; 40(2):171-6. PMC: 4810018. DOI: 10.1177/1753193414535720. View

11.

Nanchahal J, Ball C, Rombach I, Williams L, Kenealy N, Dakin H . Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2022; 4(6):E407-E416. PMC: 7613263. DOI: 10.1016/S2665-9913(22)00093-5. View

12.

Ryan V, Brown H, Minns Lowe C, Lewis J . The pathophysiology associated with primary (idiopathic) frozen shoulder: A systematic review. BMC Musculoskelet Disord. 2016; 17(1):340. PMC: 4986375. DOI: 10.1186/s12891-016-1190-9. View

13.

Buchbinder R, Green S, Youd J . Corticosteroid injections for shoulder pain. Cochrane Database Syst Rev. 2003; (1):CD004016. PMC: 6464922. DOI: 10.1002/14651858.CD004016. View

14.

Bastien C, Vallieres A, Morin C . Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001; 2(4):297-307. DOI: 10.1016/s1389-9457(00)00065-4. View

15.

Rangan A, Brealey S, Keding A, Corbacho B, Northgraves M, Kottam L . Management of adults with primary frozen shoulder in secondary care (UK FROST): a multicentre, pragmatic, three-arm, superiority randomised clinical trial. Lancet. 2020; 396(10256):977-989. DOI: 10.1016/S0140-6736(20)31965-6. View

16.

Williams Jr J, Holleman Jr D, Simel D . Measuring shoulder function with the Shoulder Pain and Disability Index. J Rheumatol. 1995; 22(4):727-32. View

17.

Hopewell S, Keene D, Marian I, Dritsaki M, Heine P, Cureton L . Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of patients with rotator cuff disorders (GRASP): a multicentre, pragmatic, 2 × 2 factorial, randomised controlled trial. Lancet. 2021; 398(10298):416-428. PMC: 8343092. DOI: 10.1016/S0140-6736(21)00846-1. View

18.

Teare M, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters S . Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: a simulation study. Trials. 2014; 15:264. PMC: 4227298. DOI: 10.1186/1745-6215-15-264. View

19.

Hopewell S, Kenealy N, Knight R, Rangan A, Dutton S, Srikesavan C . Anti-TNF (adalimumab) injection for the treatment of adults with frozen shoulder during the pain predominant stage protocol for a multi-centre, randomised, double blind, parallel group, feasibility trial. NIHR Open Res. 2023; 2:28. PMC: 10593336. DOI: 10.3310/nihropenres.13275.2. View

20.

Hand C, Clipsham K, Rees J, Carr A . Long-term outcome of frozen shoulder. J Shoulder Elbow Surg. 2007; 17(2):231-6. DOI: 10.1016/j.jse.2007.05.009. View