Overwhelming Evidence for Continuing TNFi after RA

August 19, 2016

Rheumatoid arthritis patients who are in remission or have stable low disease activity should continue TNFi therapy to control flares, study finds.

In the largest randomized controlled trial to date that assesses the safety and efficacy of stopping TNFi therapy in rheumatoid arthritis (RA) patients who are in remission or have stable low disease activity, researchers find overwhelming evidence for continuing TNFi (tumor necrosis factor inhibitor) therapy to control flares.

“We have demonstrated that stopping treatment with TNFi in patients with established RA in remission or with stable low disease activity results in significantly more flares than does continuation of TNFi,” wrote the researchers who described the findings as both statistically and clinically significant. The findings appear in the July 27 issue of Arthritis and Rheumatology.

Current treatment guidelines recommend that rheumatoid arthritis patients begin a course of disease modifying antirheumatic drugs (DMARDs) with or without a biologic at the first sign of flares. The theory is that the sooner treatment is started, the greater the likelihood of reaching a sustained remission.

The American College of Rheumatology 2015 rheumatoid arthritis treatment guidelines suggest that for patients with established RA with low disease activity, or for patients who are in remission, DMARD, TNFi, non-TNF biologic or tofacitinib therapy be continued. These recommendations are based on clinical observations and experience that suggest that only a small minority of patients with low disease activity (not remission) are able to successfully discontinue all RA therapy. And, if all RA therapies are discontinued, flare risks are high.

Once the disease is in remission or has reached a stable low disease status, some physicians opt to taper TNFi biologic agents because they are associated with the increased risk of infections and, possibly, some forms of cancer, the authors wrote. There is also the issue of cost, which is substantial as compared to treatment with conventional synthetic DMARDs.

But in terms of the effects on health outcomes, the results have been mixed. A few small studies have examined the effects of stopping TNFi treatment once patients have reached remission. One study suggested that 73.4% of 717 RA patients did well for more than 12 months after stopping their first TNFi. The HONOR study found that 48% of 75 RA patients in maintained remission and 62% maintained low disease activity for at least 12 months. Other studies have looked at dose reduction, which generally worked better to control recurring flares than stopped TNFi therapy altogether.

The new study, a nationwide multicenter, open-label randomized controlled trial, included 531 rheumatoid arthritis patients who stopped TNFi therapy once they reached remission or stable low disease activity. A second group of 286 patients, continued to take a TNFi therapy. At 12 months, patients who stopped TNFi treatment had a greater than three-fold (51.2% of 531 patients) increased risk of experiencing a flare as compared to the group that continued TNFi treatment (18.2% of 286 patients).

The hazard ratio for occurrence of a flare after stopping TNFi was 3.50 (95% confidence interval [95% CI] 2.60–4.72).

The level of disease activity according to the mean DAS28 was significantly increased in the stop group compared to the continuation group throughout the follow-up period, although the vast majority of patients remained well below the threshold for moderate disease activity.

After restarting TNFi treatment, most patients in the stop group (84.6% of 195 patients) quickly regained low disease activity or remission. They regained a DAS28 of <3.2 by 6 months. The median time to a regained DAS28 of <3.2 was 12 weeks (95% Cl 10.7–13.3).

There were no notable safety issues associated with stopping and restarting TNFi, but the total number of hospitalizations was significantly higher in the stop group than the continuation group (6.4% versus 2.4%).

 

References:

Marjan Ghiti Moghadam, Harald E. Vonkeman, et al. “Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open-Label Randomized Controlled Trial,” Arthritis and Rheumatology. July 27, 2016. DOI: 10.1002/art.39626

 

Jasvinder A. Singh, Kenneth Saag, et at.  “2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis,” Arthritis Care and Research. DOI 10.1002/acr.22783