Immune Modulators OK During Surgery in Most Psoriasis, PsA

Janis C. Kelly

August 05, 2016

Most patients with psoriasis and psoriatic arthritis (PsA) undergoing low-risk surgery can safely continue immunomodulatory drugs throughout, National Psoriasis Foundation (NPF) experts report in an article published online July 23 in the Journal of the American Academy of Dermatology.

Young M. Choi, MD, from the Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, California, and colleagues stress that this recommendation applies to infliximab, adalimumab, etanercept, methotrexate, and cyclosporine, but not (yet) to newer agents. The authors also warn that this advice does not apply to patients undergoing moderate-risk or high-risk procedures, who should be managed with consideration of individual risk factors and comorbidities.

Lindsay Strowd, MD, assistant professor of dermatology at Wake Forest Baptist Health, Winston-Salem, North Carolina, told Medscape Medical News, "I think the article by Choi et al is intriguing in that it challenges the long-held notion of systemic immunosuppressive medications presenting a risk to patients in the perioperative period. The level of evidence cited by this study is considered level III, meaning there is a need for large, randomized prospective trials examining psoriasis patients in the perioperative period both on and off systemic medications." Dr Strowd was not involved in the study.

This new guidance from the NPF Medical Board marks a clear change from previous recommendations on perioperative management of immunomodulatory treatment for rheumatology patients from groups in the United States, Canada, the United Kingdom, France, and Japan, all of which said that such drugs should be stopped well in advance of surgery.

Steven Daveluy, MD, assistant professor of dermatology, Wayne State University, Dearborn, Michigan, told Medscape Medical News, "I was very pleased to read the updated recommendations from Choi et al and the National Psoriasis Foundation. I think their reasoning was sound and nothing major was overlooked. They included not only data regarding patients with psoriasis and psoriatic arthritis but also patients with rheumatoid arthritis and inflammatory bowel disease treated with the medications perioperatively. This allowed them to include evidence from more patients, which adds strength to the recommendations." Dr Daveluy was not involved in the study.

The authors explain that the practice of withholding systemic immunomodulatory agents grew out of concern that increased risk for infection associated with such drugs might be increased by immune suppression and reduction in cell-mediated Immunity associated with surgical stress. This potential risk had to be balanced against the proven risk for psoriasis flare associated with discontinuing biologicals for the recommended period, which can be up to 16 weeks.

For patients with psoriasis and PsA, there were few studies to support this practice, and the potentially negative trade-off was brought into sharp relief by retrospective data from Bakkour et al showing that patients with psoriasis and PsA treated with tumor necrosis factor (TNF)-alpha inhibitors or interleukin (IL)-12/23 inhibitors had significantly more postsurgical complications if treatment was stopped than if it continued through surgery.

Partly in reaction to the Bakkour et al data, Dr Choi and colleagues at the NPF undertook a literature review and analysis of studies addressing the use of methotrexate, cyclosporine, and targeted immunomodulators in patients undergoing surgery. The targeted agents included TNF-alpha inhibitors, IL-12/23 inhibitors, and IL-17 inhibitors.

The reviewers examined 46 studies, most of which were retrospective studies in patients with rheumatoid arthritis or inflammatory bowel disease. "We believe that there is sufficient evidence that [infliximab], adalimumab, etanercept, [methotrexate], and cyclosporine should be safely continued through low-risk operations. For intermediate- and high-risk operations, a case-by-case approach should be taken based on the patient’s individual risk factors and comorbidities," the authors conclude.

The NPF experts further recommend that in cases where TNF-alpha inhibitors will be discontinued, the patients have perioperative treatment with oral methotrexate or cyclosporine to prevent psoriasis flares. They also note that no recommendations were possible for perioperative use of golimumab certolizumab pegol, ustekinumab, apremilast, secukinumab, or ixekizumab because of insufficient data.

New Guidance Expected to Change Clinical Practice in Psoriasis and PsA

Dr Daveluy found the data strong enough to support moving away from presurgical discontinuation of immunomodulatory drugs for patients with psoriasis and PsA. He said, "When medications are new, I agree that a cautious approach is warranted. Now that we have good evidence that there is no risk to continuing these medications preoperatively, and there is a clear risk of disease flare when the medication is discontinued, it would be a disservice to our patients to stop them unnecessarily. With the TNF-alpha inhibitors (infliximab, etanercept, adalimumab), there is also evidence that interruptions in therapy can lead to a loss of effectiveness of the medications."

The change in recommendations might foster further research, which could help improve care for patients facing moderate- or high-risk surgeries, Dr Daveluy added.

"As Choi et al pointed out, many of the biologics used to treat psoriasis have a longer half-life, meaning they require discontinuation several weeks to months prior to a procedure if adhering to the current guidelines. This places patients at risk for disease flares, which can also complicate surgical procedures and at times lead to postponement of the procedure," Dr Strowd explained. "In my own practice, I have had multiple patients with psoriasis who were unable to undergo knee or hip replacement due to active psoriasis overlying the affected joint. I believe this article is a good first step towards challenging the status quo of the current guidelines and serves to encourage the medical community to conduct more meaningful studies regarding this matter."

Dr Choi and one coauthor have disclosed no relevant financial relationships. Other coauthors disclosed serving as consultants or on speaker's bureaus for AbbVie, Amgen, Celgene Corporation, Dermira, Janssen, Novartis, Pfizer, Regeneron, Eli Lilly, and Sun Pharmaceutical Industries; research funding from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Coherus Biosciences, Celgene Corporation, Dermira, Janssen, Merck, Novartis, Eli Lilly, LEO Pharma, Pfizer, and Sun Pharmaceutical Industries. One coauthor is employed by the National Psoriasis Foundation, which receives unrestricted financial support from companies that make products used to treat psoriasis and psoriatic arthritis, including AbbVie, Amgen Inc, Celgene Corporation, Eli Lilly and Co, Galderma Laboratories LP, Janssen Biotech Inc, LEO Pharma Inc, Novartis, Pfizer Inc, and Stiefel, a GSK Company. Dr Strowd and Dr Daveluy have disclosed no relevant financial relationships.

J Am Acad Derm. Published online July 23, 2016. Abstract

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