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Efficacy and safety of intra-articular therapies in rheumatic and musculoskeletal diseases: an overview of systematic reviews
  1. Sebastián Cruz Rodriguez-García1,
  2. Raul Castellanos-Moreira2,
  3. Jacqueline Uson3,4,
  4. Esperanza Naredo5,6,
  5. Terence W O'Neill7,
  6. Michael Doherty8,
  7. Mikael Boesen9,
  8. Hemant Pandit10,
  9. Ingrid Möller Parera11,12,
  10. Valentina Vardanyan13,
  11. Lene Terslev14,
  12. Will Uwe Kampen15,
  13. Maria Antonieta D'Agostino16,17,
  14. Francis Berenbaum18,19,
  15. Elena Nikiphorou20,21,
  16. Irene Pitsillidou22,
  17. Jenny de la Torre-Aboki23 and
  18. Loreto Carmona24
  1. 1Rheumatology, Hospital Universitario de la Princesa, Madrid, Spain
  2. 2Rheumatology, Hospital Clinic de Barcelona, Barcelona, Spain
  3. 3Rheumatology, Hospital Universitario de Mostoles, Madrid, Spain
  4. 4Medicine, Universidad Rey Juan Carlos, Madrid, Spain
  5. 5Rheumatology, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain
  6. 6Rheumatology - Joint and Bone Research Unit, Hospital Universitario Fundación Jiménez Díaz, IIS Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
  7. 7Rheumatology, Centre for Epidemiology Versus Arthritis, University of Manchester & NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK
  8. 8Medicine, University of Nottingham, Nottingham, UK
  9. 9Radiology, Copenhagen University Hospital Bispebjerg- Frederiksberg, Copenhagen, Denmark
  10. 10University of Leeds, Leeds, UK
  11. 11Facultad de Medicina y Ciencias de La Salud, Universidad de Barcelona, Barcelona, Spain
  12. 12Rheumatology, Instituto POAL de Reumatología, Barcelona, Spain
  13. 13Rheumatology, Yerevan State Medical University after Mkhitar Heratsi, Yerevan, Armenia
  14. 14Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark
  15. 15Nuclear Medicine, Radiologische Allianz, Hamburg, Germany
  16. 16Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  17. 17Faculty of Medicine and Surgery, Catholic University of the Sacred Heart, Rome, Italy
  18. 18Rheumatology, AP-HP Saint-Antoine hospital, Paris, France
  19. 19Sorbonne University - INSERM CRSA, Paris, France
  20. 20Centre for Rheumatic Diseases, King's College London, London, UK
  21. 21Rheumatology Department, King's College Hospital, London, UK
  22. 22EULAR PARE Patient Research Partner, Nicosia, Cyprus
  23. 23Rheumatology, Hospital General Universitario de Alicante, Alicante, Spain
  24. 24InMusc, Madrid, Spain
  1. Correspondence to Dr Sebastián Cruz Rodriguez-García; sebastiancruz.rodriguez{at}


Objective To summarise the evidence on intra-articular therapies (IAT) to inform the 2020 EULAR recommendations.

Methods An overview of systematic reviews (SR) including randomised-controlled trials (RCTs) of IAT in adults with arthropathies was performed up to July 2020. Pain, function, and frequency of adverse events were the main efficacy and safety outcomes, respectively. Quality was assessed with the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool.

Results Of 184 references identified, 16 met the inclusion criteria, and a search of their reference lists identified 16 additional SRs. After quality assessment, 29 were finally included. Of these, 18 focused on knee osteoarthritis (KOA), 6 on hip osteoarthritis (HOA), 3 on shoulder capsulitis (SC), and 3 on rheumatoid arthritis. Overall, hyaluronic acid showed a small effect on pain and function in KOA but not in HOA or shoulder capsulitis. Intra-articular glucocorticoids showed a small effect in pain and function in KOA and function in HOA and SC. Platelet-rich plasma showed benefit in pain and function in KOA but not in HOA. Mesenchymal stem cells behaved similarly. Most SR results were of moderate quality and RCTs included often presented a high risk of bias, mainly due to inadequate blinding and heterogeneous results. All interventions were well tolerated with no clear safety differences.

Conclusions This overview underlines that most IAT currently used in KOA, HOA, and SC exert small effects and are well tolerated. However, no firm conclusions can be drawn for inflammatory arthritis due to the limited data found.

  • arthritis
  • glucocorticoids
  • osteoarthritis
  • therapeutics

Data availability statement

Data are available upon reasonable request to the corresponding author.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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Data availability statement

Data are available upon reasonable request to the corresponding author.

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  • Contributors SCR-G, RC-M, LC, JU, and EN contributed to the conception and study design. SCR-G and RC-M performed study selection and data collection. SCR-G, RC-M, LC, JU, and EN analysed the data. SCR-G, RC-M, LC, JU, EN, TWON, MD, MB, HP, IMP, VV, LT, WUK, MADA, FB, EN, IP, and JdlT contributed to the interpretation of the data. SR-G and RC-M wrote the first version of the manuscript and LC revised it critically. All authors read and approved the final manuscript.

  • Funding This study was supported by a EULAR Task force grant CL109.

  • Competing interests SCR-G reports grants from The Spanish Rheumatology Foundation during the conduct of the study, and personal fees from Roche, Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb and Novartis and non-financial support from Lilly, Pfizer, Sanofi, MSD, Abbvie, UCB-Pharma, outside the submitted work. MD has received personal fees for advisory boards from Grunenthal, Mallinckrodt and Pfizer, and author royalties from UpToDate, and was an investigator in an AstraZeneca-funded, non-drug study (the ‘Sons of Gout’ study), unrelated to this work. LT has received speakers fee from AbbVie, Janssen, Roche, Novartis, Pfizer, MSD, BMS and GE. FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Serono, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, outside the submitted work. LC declares that her institute receives grants for studies and research courses from Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA.

  • Provenance and peer review Not commissioned; externally peer reviewed.