Background: The pharmacotherapy for rheumatoid arthritis (RA) has dramatically advanced with the introduction of biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). However, even when adhering to the recommendation [1], a significant number of patients with established RA still exhibit some signs and symptoms. In 2021, EULAR defined these patients as having ‘difficult-to-treat’(D2T) RA [2], which affects 10.1% of patients with RA [3] and leads to progressive functional impairment over time. It has been stated that an individual management approach for patients with D2T RA is needed considering non-pharmacological interventions [4].

Objectives: To elucidate the therapeutic effect of orthopaedic surgical intervention (OSI) in patients with D2T RA.

Methods: A total of 995 patients with RA underwent OSI at Niigata Rheumatic Center between 2016 and 2022 and were followed for 12 months after surgery. OSI was performed in patients with functional disabilities caused by structural damage to the affected joints. Following the EULAR definition of D2T RA [2], patients who met its criteria in the preoperative state were selected excluding surgeries other than the most recent surgery, data missing and no revisit. According to the surgical site, hand, wrist, and foot surgeries were classified into the small joint surgery (SJS) group, and other joint surgeries were classified into the intermediate and large joint surgery (IJS+LJS) group. The mean DAS28-ESR at baseline, 6 months and 12 months after surgery was calculated and divided into two groups: remission (REM) + low disease activity (LDA) group and moderate disease activity (MDA) + high disease activity (HDA) group. The evaluation items included surgical site, results of blood and biochemical tests, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Disease Activity Score for 28 Joints (DAS28)-ESR, Face scale and Patient’s assessment of general health (GH). The use of drugs such as prednisolone (PSL), methotrexate (MTX), and b/tsD-MARDs, and comorbidities were investigated.

Results: After excluding the exclusion criteria, 74 (14.4%) of 534 recent surgical cases were diagnosed with D2T RA. The mean age at surgery was 64.3 years, the male/female ratio was 10/64, and the mean duration of RA was 18.3 years. The numbers of the SJS and IJS+LJS groups were 50 and 24, respectively. The number of the REM+LDA and MDA+HAD groups were 51 and 23, respectively. The mean number of previous b/tsDMARDs at baseline was 2.8, and b/tsDMARD switching was performed in 21 patients during the 12-month follow-up period. There were no significant changes in the number of patients using PSL and MTX and their dosage during the follow-up period. The comorbidities were hypertension: 23, respiratory disease: 21, chronic kidney disease: 21, liver disease: 8, diabetes: 7 and others: 7. The baseline mean HAQ-DI and DA28-ESR significantly decreased from 1.05 and 2.9, respectively, to 0.88 and 2.4 at 12 months postoperatively (p<0.01). Neither showed a significant interaction, suggesting that the improvement in HAQ-DI was due to OSI rather than reduced disease activity. While FS did not change significantly from 8.9 to 7.7, GH decreased from 37.4mm to 25.6mm (p<0.01). The mean HAQ-DI in the IJS+LJG group significantly decreased from 1.36 to 1.11 (p<0.01), and in the REM+LDA group it significantly decreased from 0.87 to 0.69 (p<0.01). Functional remission rate (HAQ-DI<0.05) increased from 23% to 37.5%. The magnitude of improvement of HAQ-DI was related to baseline GH and anti-cyclic citrullinated peptide antibody (ACPA) titer. Patient age, disease duration and the number of previous b/tsDMARDs used were associated with HAQ-DI at 12 months after surgery.

Conclusion: In the absence of effective pharmacological treatment strategies, OSI directly improves physical function and represents a viable treatment option for D2T patients with structural joint damage.

REFERENCES: [1] Smolen JS, Breedveld FC, Burmester GR et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 2016;75:3-15.

[2] Nagy G, Roodenrijs NMT, Welsing PM et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31-5.

[3] Takanashi S, Kaneko Y, Takeuchi T. Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical practice. Rheumatology 2021;60(11):5247-56.

[4] de Hair MJH, Jacobs JWG, Schoneveld JLM, et al. Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology (Oxford) 2018;57(7):1135-44.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.