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Treatment Recommendations for RA in Cancer Fail to Meet Criteria
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Treatment recommendations for rheumatoid arthritis among patients with cancer “often fail” to meet expected criteria methodology, and although there is broad support for exercising caution when prescribing disease-modifying antirheumatic drugs, there remains a lack of consensus in other area, according to data published in Arthritis Care & Research.
“Our study is the first systematic review synthetizing the recommendations from organizations all over the world about the management of patients with rheumatoid arthritis and cancer,” Maria A. Lopez‐Olivo, MD, PhD, and Maria E. Suarez-Almazor, MD, PhD, both of the University of Texas MD Anderson Cancer Center, told Healio Rheumatology.
“Tumor immunity plays a major role in controlling cancer progression, this is particularly important as most drugs required for the treatment of RA are immunosuppressant,” they wrote in the article. “Previous studies have reported on recommendations for the management of comorbidities in patients with RA, but the level of consensus regarding management of cancer has not been studied.”
To analyze recommendations for the management of RA in patients with cancer, Lopez-Olivo and colleagues conducted a search of electronic databases, guideline registries and relevant websites, including CINAHL, Cochrane, EMBASE, Medline, PubMed and Web of Science. The researchers considered all clinical practice guidelines regarding the use of DMARDs for RA, that were drafted through a consensus process and published after 2000, for inclusion. The search strategy was developed with the help of an experienced health sciences librarian.
The search netted a total of 6,266 records, including 4,077 nonduplicate entries. Of those unique records, the researchers evaluated 358 full-text articles for eligibility, resulting in the inclusion of 39 recommendations from 14 countries in the final analysis. The researchers selected and analyzed the recommendations using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and later searched for similarities and discrepancies among recommendations.
According to the researchers, just 17 of the 39 recommendations described their methods for reaching a consensus, and 21 reported funding sources. A total of 31 recommendations, or 79% addressed cancer risk in RA. The average scores for AGREE II domains ranged from 33% to 87%. In addition, the included recommendations failed to agree on the safety of DMARD use for RA in patients with cancer, save for the contraindication of TNF inhibitors among patients who at risk for lymphoma.
However, most recommendations agreed that providers should cease and re-evaluate RA treatment in the event of a new cancer diagnosis. Treatment recommendations for patients with a history of cancer varied based on the drug, cancer type and time since diagnosis. Overall, few recommendations addressed all issues relevant to RA in patients with cancer.
“This is an area where there are many unresolved questions, and the current guidance does not adequately address management for individual patients,” Lopez-Olivo and Suarez-Almazor said. “Important issues such as cancer stage, or the age of the patient, are not considered.”
“Recommendations should be different for different scenarios of patients with RA, such as an older woman with resected stage-1 estrogen-positive breast cancer compared with a young patient with advanced melanoma who will receive immune checkpoint inhibitors,” they added. “Our report can help national and international organizations identify gaps and disagreements to generate evidence data and develop specific recommendations that can be used for a more personalized guidance in the management of patients with RA and concomitant cancer.” – by Jason Laday
Disclosure: Lopez-Olivo reports no relevant financial disclosures. Please see the study for all other relevant financial disclosures.
Perspective
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David A. McLain, MD, FACP, FACR
As a clinician, what do you do with a rheumatoid arthritis patient that develops cancer while on therapy? We know that prior studies have shown that RA patients have an overall cancer risk that is 10% higher than the general population. Is the cancer related to the patients underlying genetics and susceptibility or is it related to the RA therapy?
I was faced this situation when I had a middle-aged female with RA who was doing very well on a TNF inhibitor biologic DMARD. While on treatment, she developed a plasmacytoma. I contacted her oncologist and he told me to continue the TNF inhibitor. About a year later, she had developed multiple myeloma. I contacted her oncologist and he said, “This progression from a plasmacytoma to multiple myeloma is part of the natural history. Continue with the TNF inhibitor.” We continued with the TNF inhibitor and her RA did very well
Six months later, she returned and told me that they were considering a bone marrow transplant for the multiple myeloma, which she went on to have. I called her oncologist and he said to continue the RA therapy. She did well with the procedure but succumbed to multiple myeloma within a year after the transplant. I wondered if the TNF inhibitor played any role in this; her oncologist told me that this was the natural history of multiple myeloma and he didn’t think so.
In the present review article, the researchers searched the literature for recommendations regarding RA therapy in those patients with the new onset of cancer, those at risk for cancer, and those with recent (<5 year) or distant (>5 years) cancer. They found 39 recommendations from 14 countries and 6 international collaborations and evaluated both conventional synthetic DMARDs and biologic DMARDs.
There was general agreement on the need for screening for cancer prior to RA therapy initiation, but disagreement on the comprehensiveness of the screening, which surprised me. We screen for TB and hepatitis B before TNF inhibitor biologic DMARDs, but I haven’t heard that we should be screening for malignancy.
Eleven recommendations unequivocally directed practitioners to discontinue biologic DMARD treatment with the onset of cancer. Several recommendations said the clinician should inform the patient of the potential for a worsened cancer outcome with continuation of the RA therapy; owing to fears of increased infection rates and possible interactions with chemotherapy, it was agreed that DMARDs are contraindicated or should be avoided in patients with active cancer.
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