TNF Inhibitor Drug Tapering Successful in Some Patients with RA

MADRID—Scores on the Health Assessment Questionnaire for Rheumatoid Arthritis (HAQ) and C-reactive protein (CRP) levels were independent predictors of whether patients could be tapered successfully from a TNF inhibitor after having reached remission of their RA, according to findings presented in a session at the Annual European Congress of Rheumatology.

Researchers also developed a composite index of several factors they say could help predict successful tapering.

It was one of two studies that highlighted the potential to withdraw certain patients from therapy in a session that also included a comparison of the effectiveness of anti-TNF drugs after a year of use.

In the Spacing of TNF-Blocker Injections in Rheumatoid Arthritis Study (STRASS), 137 patients in sustained remission with a DAS28 of less than 2.6 for at least six months were randomized to keep taking their TNF inhibitor at their full dose or to space their injections gradually until they were discontinued, said Thao Pham, MD, PhD, professor of rheumatology at Saint Marguerite Hospital in Marseille, France.¹ Successful tapering was reached when patients were able to whittle to 25% of their regimen.

Two variables differed between those for whom TNFi tapering was successful and for whom it wasn’t. Patients with success had an HAQ of 0.3, compared with 0.89 (P=.01), and the successes had a CRP reading of 2.35 mg/L, compared with 3.48 mg/L (P=.02).

More studies are needed to accurately identify patients who can safely be taptered off TNF inhibitors, such as etanercept and adalimumab.
Martin Shields / Science Source

Researchers found that an HAQ threshold of at least 1.125 predicted a successful tapering with a specificity of 93% and an area under the curve (AUC) of 0.713 (confidence interval [CI]: 0.54–0.87). A CRP threshold of at least 6.8 mg/L had a specificity of 0.97 and an AUC of 0.689 (CI: 0.55–0.83). Dr. Pham acknowledged that these AUCs were “not satisfying.”

A composite that includes anti-citrullinated protein antibody (ACPA) status, Simplified Disease Activity Index (SDAI) scores, CRP and HAQ also may be predictive, researchers said. They found a score threshold that predicted successful tapering, with a specificity of 100%, a sensitivity of 54% and an AUC of 0.829 (CI: 0.67–0.99).

“A validation study will be need to confirm its ability to select patients for treatment decrease,” Dr. Pham said.

Withdrawing DMARD Therapy

In interim results from another study examining the possibility of reducing therapy, Canadian researchers found that withdrawing certain patients from non-biologic disease-modifying anti-rheumatic drug (nbDMARD) therapy yielded responses that were just as good as those who continued on both those DMARDs and certolizumab pegol.²

In the real-life, open-label trial, researchers randomized 79 patients who had had certolizumab pegol added to their treatment after having an inadequate response to nbDMARDs, including methotrexate (MTX) and other drugs. On the combination, the patients had had at least a 1.2-point improvement on the DAS28-ESR scale.

At either three or six months, patients were randomized to stay on the combination or to have the nbDMARD removed, and then they were followed for 18 months. Patients had the option to stay on their nbDMARD, even if they met the criteria for having it withdrawn. Thirty-five patients were in the combination group and 44 in the monotherapy group. There were no significant differences between the groups in age, gender, rheumatoid factor status or experience with prior biologics.

After 18 months, with adjustments made for baseline scores, similar improvements were seen for the groups on DAS28-ESR, with an improvement of 2.1 points in the combination group and 2.0 points for the monotherapy group, said Janet Pope, MD, MPH, chair of rheumatology at St. Joseph’s Health Care in London, Ontario, who cautioned these were interim data only and that the results should be interpreted cautiously.

Researchers also found that the odds of achieving a DAS28 low disease activity status, or an improvement of at least 1.2 points on the DAS28, or both were no different between the two groups.

“What if someone’s getting a response on certolizumab pegol in usual care with active RA, what if we withdraw their active DMARD—or not?” Dr. Pope said. “The results look very similar whether [or not] you continue background DMARDs. We will find the real results, the full data set, very soon.”

Researchers found that adding glucocorticoids to intensive treatment with biologics & methotrexate for early, aggressive RA did not produce better results & led to a higher percentage of patients who stopped their therapy because of adverse events.

Adding Glucocorticoids

In another study, researchers found that adding glucocorticoids to intensive treatment with biologics and MTX for early, aggressive RA did not produce better results and led to a higher percentage of patients who stopped their therapy because of adverse events, said Roberto Caporali, MD, professor of rheumatology at the University of Pavia in Italy.³

The trial included glucocorticoid- and MTX-naive patients with active RA for at least a year and a least one predictor of aggressive disease. All patients received adalimumab for 12 months and MTX through two years. They were randomized to get either placebo or prednisone, at 50 mg a day tapered to 6.25 mg a day.

At one year, remission—DAS28 of less than 2.6, SDAI of no higher than 3.3 and CDAI of no more than 2.8—was seen in 56.3% in the placebo group and 45.3% in the glucocorticoid group (P=.07). Researchers also found that DAS28 remission at two years was seen in 36.8% of the standard therapy group and 30.9% of the glucocorticoid group.

Among those who completed the trial, the frequency of adverse events was similar, researchers found. But in the glucocorticoid group, 16.5% of patients opted to stop therapy because of adverse events, compared with just 9.3% in the standard therapy group.

“Although these results should be tested with other biologic therapies,” Dr. Caporali said, “the high dropout rate for adverse events in the intensive group should be carefully considered in the risk–benefit ratio.”

Thomas R. Collins is a freelance writer living in South Florida.

References

1. Barral C, Hajage D, Fautrel B, et al. Tool and threshold predicting a successful biological DMARDs tapering in patients with RA remission determination (abstract OP0018). Annual European Congress of Rheumatology. 2017 Jun 14. Madrid, Spain.
2. Pope J, Rampakakis E, Grant E, et al. DMARD withdrawal in RA patients achieving therapeutic response with certolizumab pegol cobined with DMARDs: Interim results from a Canadian observational randomized study (abstract OP0019). Annual European Congress of Rheumatology. 2017 Jun 14. Madrid, Spain.
3. Caporali R, Montecucco C, Bartoloni E, et al. Induction of remission and maintenance in early, aggressive rheumatoid arthritis using adalimumab in combination with methotrexate with or without short-term high-dose glucocorticoids: Results of a Phase IV multicenter, randomized, double blind study (abstract OP0015). Annual European Congress of Rheumatology. 2017 Jun 14. Madrid, Spain.