Sustained Remission in RA Occurs, but is Poorly Reported

Jun 13, 2017

In this review, researchers document the factors most commonly associated with sustained remission in rheumatoid arthritis patients receiving anti-TNF therapy.

The use of aggressive treat-to-target strategies with biologics have dramatically improved the outcomes for patients with rheumatoid arthritis, but in a systematic review of studies designed to identify the demographic and clinical factors associated with sustained remission, researchers found that these factors are rarely documented.

Of 4,438 manuscripts that were identified from three databases for this review, only six studies met the inclusion criteria for this review, and these were observational studies.

“With the increasingly widespread use of anti-TNF therapy, and aspirations of moving towards personalized medicine, understanding which patients achieve the most profound and durable therapeutic effect is essential to ensuring high-quality and cost-effective management decisions, as well as considering the wider context in which an individual’s disease occurs,” wrote Philip Hamann, BMBS, BMedSci, of the University of Bath in the United Kingdom, and colleagues in the May 8 online issue of Arthritis Care & Research.

The aim of treatment, they wrote, is sustained remission. But not all patients respond to anti-TNF therapy. Dr. Hamann and colleagues wanted to know what factors were at play in remission. They assessed various demographic, disease and medication correlates of long-term remission finding that concomitant methotrexate use is associated with greater sustained remission for rheumatoid arthritis patients treated with an anti-tumor necrosis factor.

“A surprising finding was that no objective clinical measure (such as the swollen joint count or inflammatory marker) was associated with sustained remission,” the authors wrote. “Improvements in objective measures of disease activity may increase more uniformly in response to anti-TNF therapy in the majority of patients, whereas the more subjective components of the DAS and patient-directed outcome measures (such as the HAQ) are more variable in their response to anti-TNF therapy.”

Rheumatoid arthritis is a disease that causes pain, swelling and stiffness in the joints. In some patients, the disease also causes the joints to become damaged and deformed. Biologic agents such as anti-tumor necrosis factor have improved outcomes for patients with rheumatoid arthritis. However, responses to anti-tumor necrosis factor can vary by patient and warrant further investigation. For example, it may take several months for a physician to determine that a treatment is not working well for a patient. This long period of assessing the success of the treatment has implications for starting early treatment and achieving remission.

The European League Against Rheumatism guidelines recommend achieving remission as early as possible, with the option of tapering anti-tumor necrosis factor agents if sustained remission is achieved. Additionally, the Outcome Measures in Rheumatology guidelines suggest a six-month duration for sustained remission.

Prior systematic reviews have been limited because they only evaluated predictors of remission in rheumatoid arthritis patients at a single point in time, or via sequential point remission rates. This systematic review fills a gap in the literature by exploring the long-term benefits of anti-tumor necrosis factor and the potential correlates of sustained remission.

The study

This was a systematic review of studies published in Embase, Medline, and the Cochrane Controlled Trials Register from 2009 through 2015. The studies included only rheumatoid arthritis patients who received anti-TNF treatment. It should be noted that definitions of sustained remission differed by study, ranging from less than six months to nine months, or two consecutive visits verified to be at least six months.

The findings:

•             Increased disease duration, higher baseline DAS, increased baseline tender joint count, and a greater baseline functional impairment, were associated with a reduced likelihood of achieving sustained remission. Higher levels of baseline disease activity were associated with a reduced likelihood of achieving sustained remission using the DAS28 score and Clinical Disease Activity Index Simplified Disease Activity Index.

•             Demographic factors that appear to be negatively associated with sustained remission included female sex, increasing age ad longer disease duration. Female sex was negatively associated with DAS28 criteria sustained remission in two of the studies. Increasing age was negatively associated with sustained remission by DAS28 in three of the studies.

•             Only one clinical factor, concomitant methotrexate use, was associated with an increased likelihood of achieving sustained remission in more than one study.

•             No objective clinical measure (such as the swollen joint count or inflammatory marker) was associated with sustained remission. Subjective components of the DAS and patient-directed outcome measures (such as the HAQ) are more variable in their response to anti-TNF therapy.

It should be noted that definitions of sustained remission differed by study, ranging from less than six months to nine months, or two consecutive visits verified to be at least six months.

Articles in the review had to meet the following criteria: 1) phase three or four clinical trials, long-term extension trials, or cohort studies reported as original research in the form of journal articles;  2) adults ages 18 years with rheumatoid arthritis according to the American College of Rheumatology (ACR) 1987 or ACR/EULAR 2010 criteria; 3) report on anti-tumor necrosis factor therapy used for the treatment of rheumatoid arthritis; 4) report on at least one measure of rheumatoid disease activity using the Disease Activity Score (DAS), DAS in 28 joints (DAS28), Clinical Disease Activity Index Simplified Disease Activity Index (CDAI), ACR/EULAR remission criteria, or ACR (formerly the American Rheumatism Association) 1981 remission criteria; and 5) report on predictors of sustained remission for at least 6 months.

 

Disclosures:

This research was funded by the British Society for Rheumatology.

References:

Haman, P., Holland, R., Hirsch, K., et al. “Factors Associated With Sustained Remission in Rheumatoid Arthritis in Patients Treated With Anti–Tumor Necrosis Factor,” Arthritis Care & Research. Published online May 8, 2017. DOI:10.1002/acr.23016.

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