RA: Factors Linked With Sustained Remission Identified

Beth Skwarecki

October 03, 2016

Patients with rheumatoid arthritis who are treated with an anti-tumor necrosis factor (anti-TNF) drug and concomitant methotrexate, are more likely to have sustained remission than those treated with an anti-TNF alone, according to a new systematic review published online August 26 in Arthritis Care & Research. Women and people with greater disease activity at the start of treatment were less likely to see sustained remission, defined as remission lasting 6 months or more.

"The evidence does support the mainstream management at the moment, with methotrexate coprescription and targeting low disease activity," lead author Philip Hamann, BMBS, from the Royal National Hospital for Rheumatic Diseases and the University of Bath, United Kingdom, told Medscape Medical News.

For the review, the investigators included phase 3 and 4 clinical trials and long-term follow-up studies that reported at least one measure of disease activity and reported whether patients sustained remission for at least 6 months. Three were registry studies, one was a retrospective case note review, and two were multicenter trials, one of which was open-label and nonrandomized.

The only clinical factor associated with a greater likelihood of achieving sustained remission in more than one study was methotrexate coprescription.

Demographic factors negatively associated with remission include female sex and increasing age. The authors note that women tend to have a higher erythrocyte sedimentation rate (ESR), increasing with age, so it is possible that sex and age are confounding factors when RA is measured through scores such as the disease activity score in 28 joints (DAS28)-ESR, which takes this marker into account.

More severe disease and longer duration were also associated with a lower likelihood of sustained remission. Higher baseline disease activity, as measured by DAS28 and Clinical Disease Activity Index (CDAI) scores, was associated with lower likelihood of sustained remission in four of the six studies. A greater number of tender joints was associated with a lower likelihood of sustained remission in two studies.

Two studies reported on disease duration at the start of treatment and found that shorter duration was associated with a greater likelihood of achieving sustained remission. One study found that an early response to treatment, by 16 weeks, was associated with a greater likelihood of sustained remission. In addition, three of four studies that assessed patient-rated functional impairment found it was associated with a lower likelihood of remission.

Dr Hamann says the results suggest that objective measures of disease severity may not tell the whole story of how somebody's disease is being managed. "It may be you've treated inflammation very well, but it's not coming through in outcome measures," because the patient's experience of their disease includes fatigue or work-related stress that may be a factor in how the patient feels. "Don't forget to talk to the patient, and find out what actually it is that's maybe causing them to seem not to respond to a drug," he advises.

"It's a very interesting paper because there's very little in the literature" about sustained remission, Petros Efthimiou, MD, associate chief of Rheumatology at New York Methodist Hospital and an associate professor of medicine and rheumatology at Weill Cornell Medical College, New York City, told Medscape Medical News. He said that a lack of data is also the review's main limitation.

Although the researchers found thousands of papers reporting on remission in RA, most only evaluated remission at a single point in time, or at multiple points without identifying whether the same patients were in remission at each point. In the end, only six studies, totaling 7476 patients, qualified for inclusion.

"Ideally, we'd like to get an evidence base to personalize treatment," said Dr Hamann, as currently it can take months to figure out whether a treatment is not working. He pointed out that a useful next step would be finding factors associated with remission in other high-cost drugs such as rituximab and tocilizumab. "It may be that there's a slightly different profile of patients who [do] better on each treatment."

Studies on point remission suggest that signaling inhibitors may work as well on their own as they do with methotrexate, said Dr Efthimiou, so he is curious whether those results apply to long-term remission.

One of Dr Hamann's coauthors has received honoraria of less than $10,000 from Pfizer and AbbVie. The other authors and Dr Efthimiou have disclosed no relevant financial relationships.

Arthritis Care Res. Published online August 26, 2016. Abstract

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