Introduction
The treatment of autoimmune rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and lupus has advanced with the use of disease-modifying anti-rheumatic drugs (DMARDs), leading to improved survival, symptom control, and functional outcomes. Despite a decline in small joint surgeries among rheumatoid arthritis patients, the need for large joint replacements remains steady. Studies show that most patients undergoing joint replacement continue methotrexate or other conventional DMARDs, indicating their central role in disease control.
However, patients with autoimmune rheumatic diseases still experience higher postoperative infection rates, likely due to underlying immune dysregulation rather than DMARD use alone. Managing DMARDs during the perioperative period poses a challenge — continuing therapy may raise infection risk, while stopping it could trigger disease flare-ups. This review aims to evaluate current clinical practice guidelines on the perioperative management of DMARDs in patients with rheumatic diseases to help optimize surgical outcomes.
Methods
This review was conducted as a scoping review to gather available information from diverse sources and identify knowledge gaps, following the JBI Scoping Review Methodology and the PRISMA-ScR Checklist. Comprehensive searches were performed in Medline and EMBASE, supplemented by manual reference checks. Titles and abstracts were screened by multiple reviewers, and full-text selection was based on predefined inclusion and exclusion criteria. Included publications were guideline-type documents from recognized rheumatology societies (2014–2024) addressing adult RA, AS, PsA, JIA, or SLE, and covering csDMARDs, bDMARDs, or tsDMARDs. Glucocorticoids and non-English publications were excluded.
Data extraction was carried out by two reviewers, collecting key details such as publication year, country, diseases covered, conflict of interest statements, panel composition, evidence systems, and included DMARDs. Specific recommendations on perioperative DMARD management were extracted and refined collaboratively to ensure accuracy and consistency, with a detailed data extraction framework provided in the supplementary file.
Characteristics of included guidelines
A total of 12 guidelines published between 2014 and 2024 were included. Most originated from Europe (n = 5, 42%) and the Asia-Pacific region (n = 5, 42%), with the remaining (n = 2, 17%) from North America. Only 2 (17%) were standalone perioperative DMARD guidelines, while 10 (83%) incorporated recommendations within broader rheumatology guidelines. Rheumatoid arthritis (RA) was the primary focus in 6 (50%) guidelines. Recommendations for csDMARDs were included in 8 (67%), bDMARDs in 8 (67%), and tsDMARDs in 5 (42%). Additionally, 3 (25%) guidelines included recommendations for glucocorticoids, and another 3 (25%) addressed other drugs such as apremilast, mycophenolate mofetil, cyclosporin A, azathioprine, tacrolimus, and biologics like ustekinumab and secukinumab. Funding sources were disclosed in 6 (50%) guidelines, and conflicts of interest were reported in 10 (83%).
Results
Recommendations regarding conventional synthetic DMARDs (csDMARDs)
Of the 8 guidelines addressing perioperative management of csDMARDs [10–15, 17, 19], all (8, 100%) included methotrexate, while 4 (50%) each covered hydroxychloroquine, sulfasalazine, and leflunomide. Three (38%) guidelines provided recommendations only for methotrexate. The strength of recommendations was weak/conditional in 4 (50%) and unspecified in 4 (50%). There was full agreement (100%) on continuing hydroxychloroquine and sulfasalazine, 75% agreement for leflunomide, and 88% agreement for methotrexate (with one suggesting a 1-week hold pre-surgery). Evidence quality was generally low, especially for non-elective or non-orthopaedic surgeries, though panel agreement ranged from 70–100% across 3 of the 8 guidelines.
Recommendations regarding biological DMARDs (bDMARDs)
Eight guidelines addressed perioperative use of bDMARDs, covering both TNF inhibitors and non-TNF agents like abatacept, tocilizumab, and anakinra. Rituximab was included in five guidelines. The strength of recommendations was weak/conditional in 5 (63%), unspecified in 2 (25%), and moderate in 1 (13%), all based on low-certainty evidence. Panel agreement was high (70–100%) in 3 of the 8 guidelines.
Temporary discontinuation of bDMARDs was conditionally recommended in 6 (75%) guidelines, considering patient and surgical factors. Timing of surgery after discontinuation varied — from “3–5 half-lives” to “1–2 months before surgery” or “one dosing cycle prior.” For rituximab, surgery was advised 3–7 months after the last dose. Recommencement was generally based on wound healing and infection absence, with 3 (38%) suggesting restart 14 days post-op. The latest guideline suggested continuation during the perioperative period.
Recommendations regarding targeted synthetic DMARDs (tsDMARDs)
Five guidelines included recommendations for tsDMARDs, with four (80%) giving conditional recommendations and one unspecified. Evidence quality was very low, though agreement was high (70–100%) in three guidelines. Patient and surgical factors guided decisions on temporary discontinuation. Timing varied across three (60%) guidelines, advising discontinuation 3–7 days before surgery and restarting 4–14 days post-op, depending on wound healing and infection status.
Other recommendations for drugs outside of inclusion criteria
Recommendations for mycophenolate mofetil, azathioprine, cyclosporine A, and tacrolimus appeared in 3 (35%) guidelines, based on low-certainty evidence, with one using post-transplant data. One guideline included belimumab, anifrolumab, and voclosporin, depending on disease severity in lupus. A conditional recommendation to continue apremilast was noted in one guideline. For ixekizumab (2 guidelines), surgery was advised at the end of the dosing cycle, while ustekinumab, secukinumab, and guselkumab recommendations suggested surgery one week after the next scheduled dose.
Recommendations for the use of glucocorticoids
With regard to recommendations for glucocorticoids, included in 3 (25%) guidelines, temporary discontinuation was not recommended in any guideline. Two of the three guidelines recommended against stress dosing with no recommendation regarding stress dosing provided in the third.
Conclusion
Guidelines for perioperative DMARD use are widely available but show significant variation in content and evidence quality. Most are based on studies involving elective hip or knee replacements, with little evidence for other surgical types. Though there was high agreement among panel members, specific guidance on patient and surgical factors remains lacking.
Differences exist in the autoimmune conditions and DMARDs covered, with most guidelines focused on RA, limiting generalizability to other diseases. Patient involvement was minimal, and their preferences—such as prioritizing flare prevention over infection risk—remain underexplored. Variations were also noted in recommendations for non-methotrexate csDMARDs and b/tsDMARD timing, largely due to limited evidence. Overall, current guidelines are inconsistent and based on low-quality data. Future studies and updated evidence on newer DMARDs are essential to improve clarity, safety, and practical application in clinical decision-making.
References
1.Callhoff J, Weiss A, Zink A, Listing J. Impact of biologic therapy on functional status in patients with rheumatoid arthritis–a meta-analysis. Rheumatology. 2013;52(12):2127–35.
[DOI] [PubMed] [Google Scholar]
2.Choi HK, Hernán MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet. 2002;359(9313):1173–7.
[DOI] [PubMed] [Google Scholar]
3.Krause D, Schleusser B, Herborn G, Rau R. Response to methotrexate treatment is associated with reduced mortality in patients with severe rheumatoid arthritis. Arthritis Rheum. 2000;43(1):14–21. [DOI] [PubMed] [Google Scholar]
4.Nikiphorou E, Carpenter L, Morris S, MacGregor AJ, Dixey J, Kiely P, et al. Hand and foot surgery rates in rheumatoid arthritis have declined from 1986 to 2011, but Large-Joint replacement rates remain unchanged: results from two UK inception cohorts. Arthritis Rheumatol. 2014;66(5):1081–9.
[DOI] [PubMed] [Google Scholar]
5.Goodman SM, George MD. Should we stop or continue conventional synthetic (including glucocorticoids) and targeted DMARDs before surgery in patients with inflammatory rheumatic diseases? RMD Open. 2020;6(2):e001214.
[DOI] [PMC free article] [PubMed] [Google Scholar]
6.Ravi B, Croxford R, Hollands S, Paterson JM, Bogoch E, Kreder H, et al. Increased risk of complications following total joint arthroplasty in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014;66(2):254–63. [DOI] [PubMed] [Google Scholar]
7.Lin JA, Liao CC, Lee YJ, Wu CH, Huang WQ, Chen TL. Adverse outcomes after major surgery in patients with systemic lupus erythematosus: a nationwide population-based study. Ann Rheum Dis. 2014;73(9):1646–51.
[DOI] [PubMed] [Google Scholar]
8.Goodman SM, Bass AR. Perioperative medical management for patients with RA, SPA, and SLE undergoing total hip and total knee replacement: a narrative review. BMC Rheumatol. 2018;2(1):2.
[DOI] [PMC free article] [PubMed] [Google Scholar]
9.Peters M, Godfrey C, McInerney P, Munn Z, Tricco A, Khalil H. JBI manual for evidence synthesis. 2020 [cited 2023 Dec 12]. Scoping Reviews. Available from: https://synthesismanual.jbi.global/
[DOI] [PubMed]
10.Albrecht K, Poddubnyy D, Leipe J, Sewerin P, Iking-Konert C, Scholz R, et al. Perioperative management of patients with inflammatory rheumatic diseases: updated recommendations of the German society for rheumatology. Z Rheumatol. 2023;82(Suppl 1):1–11.
[DOI] [PubMed] [Google Scholar]
