Sustained Remission in RA: What the Data Say

by Nancy Walsh 
Senior Staff Writer, MedPage Today

August 31, 2016

Action Points

Use of concomitant methotrexate along with anti-tumor necrosis factor (TNF) therapy was associated with a greater likelihood of achieving sustained remission in rheumatoid arthritis, while clinical factors such as high disease activity scores had a negative association, a meta-analysis found.

Two studies were identified in the literature as having assessed the effects of concomitant methotrexate on sustained remission. In one, the odds ratio for sustained remission on the Disease Activity Score in 28 joints (DAS28) was 2.02 (95% CI 1.51 to 2.71), and in the second, the odds ratios were 2.83 (95% CI 1.18 to 6.80) for DAS28 sustained remission and 1.55 (95% CI 1 to 2.42) for the Clinical Disease Activity Index (CDAI), according to Philip Hamann, MBBS, PhD, of the University of Bath in England, and colleagues.

In contrast, several studies found that patients with higher baseline DAS28 were less likely to achieve sustained remission, with odds ratios of 0.37 (95% CI 0.19 to 0.73) in one study and 0.62 (95% CI 0.55 to 0.70) in another, the researchers reported online in Arthritis Care & Research.

"Aggressive treat-to-target strategies alongside increased use of biologic agents such as anti-TNF have improved outcomes for patients with rheumatoid arthritis, and the aim of achieving sustained remission is a realistic aspiration," they wrote.

Most studies have evaluated remission at only one time point, such as at 6 months. "However, given the chronicity of a condition such as rheumatoid arthritis and the long-term benefits of remission, a durable positive response to anti-TNF is a more clinically relevant outcome," they stated.

To identify factors associated with sustained remission, thus avoiding delays in treatment changes when a therapy is not working and accruing unnecessary costs, Hamann and colleagues conducted a systematic literature review and, when possible, a meta-analysis of potentially influential demographic, clinical, and treatment factors among patients with rheumatoid arthritis.

They identified six papers that met their inclusion criteria. All were observational, and sustained remission was typically defined as 6 to 9 months.

The highest rates of sustained remission were seen in the HONOR study, at 38.1%, while the lowest rates were in the CORRONA database, at 7.9%.

In two studies, female sex had a negative association, with odds ratios of DAS28 sustained remission of 0.57 (95% CI 0.44 to 0.75) and 0.43 (95% CI 0.23 to 0.82), while no relationship was seen in a third study. Meta-analysis of these three studies gave an odds ratio of 0.53 (95% CI 0.44 to 0.63).

Three studies reported that increasing age had a negative association with DAS28 sustained remission, with odds ratios that included 0.79 (95% CI 0.63 to 1) and 0.98 (95% CI 0.97 to 0.99).

Longer disease duration also had a negative association (OR 0.85, 95% CI 0.75 to 0.97), while response to treatment before 16 weeks had a positive association (OR 1.88, 95% CI 1.27 to 2.78).

Having a higher number of tender joints was negatively associated with sustained remission on the DAS28 (OR 0.910, P=0.031), and also on the CDAI (OR 0.96, 95% CI 0.92 to 1), but a higher swollen joint count had no association.

Baseline functional impairment measured on the Health Assessment Questionnaire (HAQ) was "consistently associated" with a lower likelihood of sustained remission, with only one study not showing an association.

Prednisone use showed a negative association with CDAI sustained remission (OR 0.69, 95% CI 0.47 to 1), as did prior use of anti-TNF therapy (OR 0.98, 95% CI 0.96 to 1).

The observation that only concomitant methotrexate was associated with sustained remission "does appear to support the practice of co-prescription of methotrexate with anti-TNF whenever possible," Hamann and colleagues commented.

"Despite the variability in both the definition of sustained remission and the predictive factors reported by each study, some common themes have emerged. One of the most striking findings was the paucity of evidence available for factors associated with sustained remission as an outcome," they wrote.

They noted that only six studies -- out of a possible 4,000 -- addressed this concern and met the inclusion criteria.

An additional knowledge gap regarding disease remission is the lack of data on many subjective components of disease, such as fatigue and mood, which can strongly influence a patient's perception of health.

Clinical studies could greatly improve therapeutic decision-making and overall patient care if more extensive information about remission were routinely collected, the authors stated.

"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 sits," they concluded.

                        Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco.

Source:                    eference: Hamann P, et al "Factors associated with sustained remission in rheumatoid arthritis in patients treated with anti-tumor necrosis factor" Arthritis Care Res 2016; DOI: 10.1002/acr.23016.