Patients with rheumatoid arthritis whose tests are rheumatoid factor-positive are more likely to discontinue treatment with tumor necrosis factor inhibitor (TNFi) therapies due to ineffectiveness, according to research published in Clinical Rheumatology.      

Researchers sought to examine the link between rheumatoid factor and anticitrullinated protein autoantibody (ACPA) status and TNFi discontinuation due to inadequate response in patients with rheumatoid arthritis. The patient cohort included those enrolled in the Japanese Tsurumai Biologic Communication Registry, an observational multicenter cohort study focused on drug retention, effectiveness, and adverse events in patients with rheumatoid arthritis who were treated with biologic therapies. Data were retrospectively collected between January 2004 and September 2008 and prospectively from October 2008 to December 2014. Patients were treated with either TNFi monotherapy or combination therapy with conventional disease-modifying antirheumatic drugs, including methotrexate, prednisolone, and tacrolimus. Patients were evaluated at baseline and at least once every 3 months thereafter. The primary end point was persistence of first-line TNFi treatment, defined as the interval between drug initiation and discontinuation due to insufficient response.

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The total cohort included 2757 patients with rheumatoid arthritis (5741 patient-years of follow up; median 2.02 years per patient; interquartile range [IQR] 0.72-4.11). Investigators identified 1237 eligible first-time TNFi users with rheumatoid arthritis with available data on both rheumatoid factor and ACPA. Nearly 500 patients (n=489) were double positive, and 75 patients were double negative. Just over 5% (5.4%) of patients were treated with TNFi monotherapy, while 94.6% received combination therapy with conventional disease-modifying antirheumatic drugs. Patients in the ACPA-positive group experienced a significantly higher discontinuation rate due to insufficient response compared with the ACPA-negative group. Cumulative discontinuation rate at 200 weeks was 23% and 13.8% in the ACPA-positive and -negative groups, respectively. Cumulative discontinuation rate among patients with rheumatoid factor-positive and -negative test results at 200 weeks was 19.8% and 16.7%, respectively. Although the difference in Disease Activity Score in 28 Joints remission at 12 months between the ACPA-positive and -negative groups was insignificant, more patients who had rheumatoid factor-negative test results achieved remission, than those whose tests results were rheumatoid factor-positive (46.0% vs 36.7%). Additionally, 85.6% and 80.5% of patients whose test were rheumatoid factor negative and positive achieved either good or moderate European League Against Rheumatism responses. Similar responses were noted in patients whose test results were ACPA-negative and positive (83.9% and 78.6%, respectively).

Study limitations include a lack of delineation of interactions of rheumatoid factor and ACPA on TNFi effectiveness, the use of physician discretion to determine the discontinuation of TNFi therapy, and a lack of information about the smoking status of patients.


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“In sum, [rheumatoid factor] positivity was strongly associated with a higher discontinuation rate of TNFi therapy owing to ineffectiveness among [rheumatoid arthritis] patients,” the researchers concluded. “[Rheumatoid factor] could be a helpful prognostic biomarker for the optimal use of TNFi in the treatment of [rheumatoid arthritis].”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference
Ogawa Y, Takahashi N, Kaneko A, et al. Association between seropositivity and discontinuation of tumor necrosis factor inhibitors due to ineffectiveness in rheumatoid arthritis [published online June 10, 2019]. Clin Rheumatol. doi: 10.1007/s10067-019-04626-x