Sarah R Kingsbury1, Puvan Tharmanathan2, Ada Keding2, Sarah J Ronaldson2, Andrew Grainger1, Richard J Wakefield1, Catherine Arundel2, Fraser Birrell3, Michael Doherty4, Tonia Vincent5, Fiona E Watt5, Krysia Dziedzic6, Terence W O'Neill7, Nigel K Arden8, David L Scott9, John Dickson10, Toby Garrood11, Michael Green12, Ajit Menon13, Tom Sheeran14, David Torgerson15, Philip G Conaghan1. 1. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds, United Kingdom (S.R.K., A.G., R.J.W., P.G.C.). 2. York Trials Unit, University of York, York, United Kingdom (P.T., A.K., S.J.R., C.A.). 3. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (F.B.). 4. School of Medicine, University of Nottingham, Nottingham, United Kingdom (M.D.). 5. Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Oxford, and Imperial College Healthcare, London, United Kingdom (T.V., F.E.W.). 6. Institute for Primary Care and Health Sciences, Arthritis Research UK Primary Care Centre, Keele University, Staffordshire, United Kingdom (K.D.). 7. Arthritis Research UK Centre for Epidemiology, The University of Manchester, NIHR Manchester Biomedical Research Centre, Central Manchester University Hospitals National Health Service (NHS) Foundation Trust, and Manchester Academic Health Science Centre, Manchester, United Kingdom (T.W.O.). 8. Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, United Kingdom (N.K.A.). 9. King's College London, London, United Kingdom (D.L.S.). 10. South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom (J.D.). 11. Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (T.G.). 12. Harrogate and District NHS Foundation Trust, Harrogate, and York Teaching Hospital NHS Foundation Trust, York, United Kingdom (M.G.). 13. Haywood Hospital, Stoke-On-Trent, United Kingdom (A.M.). 14. Cannock Chase Hospital, Cannock, United Kingdom (T.S.). 15. University of York, York, United Kingdom (D.T.).
Abstract
Background: Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse. Objective: To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis. Design: Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up. (ISRCTN registry number: ISRCTN91859104). Setting: 13 primary and secondary care centers in England. Participants: Of 316 patients screened, 248 participants (82% women; mean age, 62.7 years) with symptomatic (pain ≥4 on a 0- to 10-point visual analogue scale) and radiographic hand osteoarthritis were randomly assigned and 210 (84.7%) completed the 6-month primary end point. Intervention: Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing usual care. Measurements: The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done. Results: At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of -0.16 point (95% CI, -0.73 to 0.40 point) (P = 0.57). Results were robust to adjustments for adherence, missing data, and use of rescue medication. No significant treatment differences existed at 3, 6, or 12 months for any secondary outcomes. The percentage of participants with at least 1 joint with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power Doppler. Baseline structural damage or synovitis did not affect treatment response. Fifteen serious adverse events were reported (7 in the hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo group). Limitation: Hydroxychloroquine dosage restrictions may have reduced efficacy. Conclusion:Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis. Primary Funding Source: Arthritis Research UK.
RCT Entities:
Background: Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse. Objective: To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis. Design: Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up. (ISRCTN registry number: ISRCTN91859104). Setting: 13 primary and secondary care centers in England. Participants: Of 316 patients screened, 248 participants (82% women; mean age, 62.7 years) with symptomatic (pain ≥4 on a 0- to 10-point visual analogue scale) and radiographic hand osteoarthritis were randomly assigned and 210 (84.7%) completed the 6-month primary end point. Intervention: Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing usual care. Measurements: The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done. Results: At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of -0.16 point (95% CI, -0.73 to 0.40 point) (P = 0.57). Results were robust to adjustments for adherence, missing data, and use of rescue medication. No significant treatment differences existed at 3, 6, or 12 months for any secondary outcomes. The percentage of participants with at least 1 joint with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power Doppler. Baseline structural damage or synovitis did not affect treatment response. Fifteen serious adverse events were reported (7 in the hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo group). Limitation: Hydroxychloroquine dosage restrictions may have reduced efficacy. Conclusion:Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis. Primary Funding Source: Arthritis Research UK.
Authors: Margreet Kloppenburg; Charles Peterfy; Ida K Haugen; Féline Kroon; Su Chen; Li Wang; Wei Liu; Gwen Levy; Roy M Fleischmann; Francis Berenbaum; Désirée van der Heijde; Prashant Bansal; Ruth Wittoek; Sheng Feng; Yuni Fang; Mary Saltarelli; Jeroen K Medema; Marc C Levesque Journal: Ann Rheum Dis Date: 2018-12-14 Impact factor: 19.103
Authors: Claudia Kedor; Jacqueline Detert; Rolf Rau; Siegfried Wassenberg; Joachim Listing; Pascal Klaus; Tanja Braun; Walter Hermann; Stefan Markus Weiner; Frank Buttgereit; Gerd R Burmester Journal: RMD Open Date: 2021-07