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Conventional disease-modifying antirheumatic drugs (DMARDs) may usually be continued in patients with inflammatory arthritis or systemic lupus erythematosus (SLE) undergoing total knee or hip replacement, but the same is not necessarily true for more targeted agents, according to an updated guideline from two medical societies.

Biologic drugs and so-called JAK inhibitors should generally be stopped before arthritis patients have such procedures, and so should biologics such as belimumab (Benlysta) and immunosuppressants in patients with non-severe SLE, according to the , with Susan M. Goodman, MD, of the Hospital for Special Surgery in New York City, as lead author.

With severe lupus, however, it's generally better to keep patients on their regular immunosuppressant regimen as well as belimumab. But for patients with severe SLE taking rituximab (Rituxan), the societies recommend scheduling surgery for the final month of the drug's dosing cycle when blood levels have bottomed out.

The new guideline replaces an earlier version published in 2017 and takes account of new agents introduced in that time and better understanding of how traditional agents affect patients in the postoperative period, particularly the risk of joint infection.

In explaining the rationale for these guidelines, Goodman and colleagues noted that rheumatic disease patients are at substantially higher risk of periprosthetic infection following joint replacement relative to people without such conditions -- by 50% in the case of rheumatoid arthritis. The immunomodulatory drugs that most of these patients take surely contribute to this increased risk.

That creates a management challenge, for simply withholding all the patients' regular medications raises the likelihood of disease exacerbation. Flares may be less problematic than a deep joint infection, but the latter is relatively rare while flares are common when antirheumatic drugs are withdrawn. Thus, it becomes a question of balancing low risks of a potentially devastating complication against high risks of a lesser but still significantly adverse outcome.

For the update, committees from the two societies reviewed papers published through August 2021 addressing medication use in patients with inflammatory arthritis -- rheumatoid arthritis, psoriatic arthritis spondyloarthritis, and juvenile idiopathic arthritis -- and SLE undergoing hip and knee replacement.

The major recommendations -- all rated as conditional -- can be summarized as follows:

• Inflammatory arthritis and SLE patients may continue usual dosing with conventional DMARDs such as methotrexate, leflunomide, and hydroxychloroquine, as well as apremilast (Otezla) in the case of psoriatic arthritis.
• Arthritis patients taking biologic drugs including rituximab should stop them prior to surgery, and procedures should be scheduled for around the time the next doses would be due, to obtain some degree of washout.
• In non-severe lupus, patients should have drugs such as mycophenolate mofetil, azathioprine, cyclosporine, and tacrolimus stopped 1 week before surgery, and usual doses of belimumab and rituximab should be delayed.
• In severe lupus, conventional DMARDs as well as anifrolumab (Saphnelo) and voclosporin (Lupkynis) -- both first approved in 2021 -- should be continued at usual doses. Belimumab and rituximab can also be continued, but as mentioned above, surgery should be scheduled for late in the latter's dosing cycle.
• No changes in corticosteroid medications are generally needed.
• In all cases where regular medications were stopped, they may be restarted when surgical wounds have started to heal and no signs of infection or other complications are evident.

As with any guideline, Goodman and colleagues emphasized that these are not intended as hard-and-fast rules and clinicians should engage in shared decision-making with patients to take account of their particular preferences and circumstances. "One patient representative on the current Voting Panel noted the anxiety that patients experience around changes to their medication regimens and urged clinicians to be cognizant of this important issue," the authors wrote.

Goodman and colleagues also acknowledged significant gaps in the available evidence and called for new research, including prospective randomized trials, to "provide clearer answers" to questions about use of conventional DMARDs, for which such evidence is often lacking. "Perioperative management of biologics also needs more definitive study," they added.

Notably, the guideline update did not address other issues related to joint replacement, such as risk of venous thromboembolism and other cardiovascular events.

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