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Methotrexate in the peri-operative period

by Roberto Russo

Recently there have been a few cases in which patients of mine have been referred for orthopaedic procedures in the context of active Rheumatoid arthritis. The orthopaedic surgeon has expressed a real concern about the use of Methotrexate (MTX) in the peri-operative period, resulting in the patient being very anxious to stop the medication. This prompted a review of the literature to understand if there is any basis for this concern. My training to this point had taught me that there was no increase in peri-operative complication and as such MTX could be continued. The priority has instead been to cease or wean the Prednisone as much as possible.

My research found that the original investigation into the topic did indeed raise concern for the association between MTX and peri-operative complications. However, these studies were either retrospective or small prospective trials and as such had methodological concerns. The most robust trial on the topic was performed in 2001 by a group in Wigan lead by DM Brennan. They prospectively studied 388 patients who were divided into 3 groups:

  • Continued MTX
  • Ceased MTX for a month around the surgery
  • No prior exposure to MTX

They compared the post-operative complications between these groups for one year post surgery, including wound healing, need for revision surgery, and flares in RA. They ultimately studied 88 patients who continued MTX and 72 patients in whom the medication was withheld in the peri-operative period. The groups were similar in characteristics, being cohorts with long standing RA with high disease activity and relatively low doses of MTX (Median dose of 10mg and 7.5mg respectively). Almost 50% of each group was also taking corticosteroids, with frequent use of other DMARD medications and the presence of significant comorbidities. In summary, I feel these groups would be at high risk of peri-operative complications.


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They found between these groups that a significantly lower incidence of complication was seen in those who continued MTX. In addition, there was significantly less disease flares in the early post-operative period in the continuing MTX group. Interestingly, increased risk of complications was associated with a number of other DMARDs, including Plaquenil, as well as a number of comorbidities. The authors of the above study undertook a 10 year post surgery review and found no incidence of late complications in the continuing MTX group. However, it should be noted that relatively low doses of MTX were used, being about 10mg weekly, and that certain situations (such as combined DMARD therapy and the presence of comorbidities) presented a high risk in themselves which would warrant the cessation of MTX for a week before and after surgery.

It seems that the resolution of this question may be well served by a meta-analysis or a better-designed and larger long term RCT. Nevertheless, a literature review was performed in 2008, which concluded similar findings as stated above, being to continue the MTX. This is in alignment with the current EULAR recommendations.