Rheumatologists have criticized what they described as omissions and problems with the 2015 American College of Rheumatology guidelines for treating rheumatoid arthritis.

Although the authors ( Arthritis Care Res. 2016;68[1]:1-25 ) evaluated evidence with GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methods and solicited public feedback on core questions, the final document minimized the use of early low-dose glucocorticoids, failed to address screening for hepatitis B virus (HBV) infection before starting biologics, and underestimated their risks in patients with a history of cancer or lymphoproliferative disease, according to separate editorial letters published in Arthritis Care & Research.

Although the guidelines recommend initial methotrexate monotherapy regardless of disease activity level, “experienced clinicians know that before any effect of the methotrexate is realized, the patient will experience joint pain, swelling, functional impairment, and morning stiffness, making the patient quite miserable,” wrote Dr. Doyt L. Conn of Emory University, Atlanta. Patients will then self-treat with NSAIDs, he added ( Arthritis Care Res. 2016 Feb 11. doi: 10.1002/acr.22864 ). “Do the authors of the 2015 ACR guidelines think that NSAIDs are as effective as and safer than low dose prednisone?” Furthermore, the guidelines seem to rank tumor necrosis factor (TNF) inhibitors and non-TNF biologics above short-term, low-dose prednisone, he wrote. “Do the authors really mean that?’’

In a reply letter ( Arthritis Care Res. Feb 11. doi: 10.1002/acr.22862 ), Dr. Jasvinder A. Singh of the University of Alabama at Birmingham and guideline coauthors denied recommending a “rigid” treatment sequence. They recommend short-term, low-dose steroids any time after initial disease-modifying antirheumatic drug (DMARD) therapy if disease activity remains moderate or high, or during flares, they wrote. “The guideline does not mandate that patients must fail any particular therapy before glucocorticoid can be given. It merely suggests that a DMARD should be tried first.”

Regarding HBV screening, Dr. Leonard H. Calabrese was “disappointed” to see no changes since the 2008 ACR RA guidance ( Arthritis Care Res. Feb 11. doi: 10.1002/acr.22865 ). One biologic, rituximab, now has a black box warning for potentially fatal HBV reactivation, mandating HBV screening before its use, said Dr. Calabrese, of the Cleveland Clinic. “We suggest that the standards of screening for and prevention of HBV reactivation have changed dramatically, and assert that the ACR guidelines are accordingly overdue for changes,” he wrote.

Dr. Singh and colleagues replied that viral hepatitis screening was “vital,” but that “it was not our charge – nor was it feasible – to cover every topic relevant to the care of RA patients in this guideline.” The field lacks data on the cost-effectiveness of universally screening RA patients for HBV before starting biologics, they added. They recommended working with hepatology/gastroenterology providers to manage RA patients with chronic viral hepatitis who need potentially immunosuppressive therapies.

Finally, the guidelines cite relatively small observational studies when addressing the use of biologics in patients with a history of cancer or lymphoproliferative disorders, wrote Dr. Hasan Yazici of Academic Hospital, Istanbul, Turkey, and his associates. Interpreting these studies as negating risk is especially concerning because of “depletion of the susceptibles bias,” when one takes into consideration that one-sixth of patients with cancer have a second or higher order primary cancer; that most national registries do not differentiate between a first primary cancer and second or higher order primary cancer in their cancer incidence rates in the general population; and that RA patients on biologics probably have no cancer history. This leads to skewed results when comparing standardized incidence ratios for cancer in TNF inhibitor users versus the general population, they added ( Arthritis Care Res. 2016 Feb 11. doi: 10.1002/acr.22863 ).

Dr. Singh and colleagues responded that “the 2015 recommendations for RA treatment in persons with past lymphoproliferative disorders or solid cancers, are conditional, not strong.” Because of the lack of evidence establishing risk in these patients, the voting panel recommended treating them the same way as other patients, they added. “The panel recognized, and the readership of these guidelines should also understand, that lack of evidence of difference does not imply an evidence of lack of difference.” They called for better studies of DMARDs and biologics in RA patients with current or historical hepatitis, cancer, heart failure, and serious infections.

Going forward, the ACR is considering how to better publicize its 30-day public comment period when developing future guidelines to better capture perspectives at the beginning, instead of at the end when GRADE protocols preclude further adjustments, Dr. Singh and his associates wrote. In addition, the ACR will broaden its RA guidelines, post drafts on its website for comment, and use a “dynamic” process “to ensure timeliness, more frequent updating, online updates, and approaches to harmonize with recommendations of other professional organizations, as needed.”

None of these authors reported funding sources or conflicts of interest.



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