TARA trial: TNF inhibitor may be tapered first before csDMARDs in well-controlled RA
Flare rates appear to be similar after tapering of a tumour necrosis factor (TNF) inhibitor or a conventional synthetic disease-modifying antirheumatic drug (csDMARD) up to 9 months in patients with rheumatoid arthritis (RA) who have achieved disease control, with a nonsignificant 10-percent difference in flare rates after 1 year in favour of csDMARDs, according to data from the TARA* study.
“Nowadays, more patients with RA achieve a state of sustained remission, which makes them eligible for tapering treatment. This is reflected in current EULAR** recommendations for the management for RA. The advice is to taper DMARD therapy in patients with RA who are in sustained remission in the following ordering: glucocorticoids, biologic (b)DMARDS and csDMARDs,” the investigators said. [Ann Rheum Dis 2017;76:960-977]
“Our results and the fact that TNF blockers are more expensive than csDMARDs support aforementioned tapering order,” they added.
In TARA, 189 patients with well-controlled RA (Disease Activity Score [DAS] ≤2.4; Swollen Joint Count [SJC] ≤1) treated with both a csDMARD and a TNF inhibitor were randomized to a gradual tapering of either csDMARD (n=94; mean age, 55.9 years) or TNF inhibitor (n=95; mean age, 57.2 years).
At the 1-year follow-up, the primary outcome of cumulative flare (DAS >2.4 and/or SJC >1) rate was 33 percent in the csDMARD tapering group and 43 percent in the TNF inhibitor tapering group. This indicates that 67 percent and 57 percent of patients in the respective tapering groups still had a well-controlled RA (p=0.17). [Ann Rheum Dis 2019;doi:10.1136/annrheumdis-2018-214970]
Of the patients who flared and restarted the last effective treatment strategy, 46 percent achieved disease control within 3 months, with the number increasing to 67 percent by 6 months. Two patients (1 percent) were unable to get back in remission within the first year.
Clinical and patient-reported outcomes—such as DAS, European Quality of Life-5 Dimensions (EQ5D) and functional ability—were comparable in both tapering groups after 1 year of follow-up and over time. Furthermore, there were no significant between-group differences in adverse events or radiological progression.
CsDMARD was tapered by cutting the dosage into half, a quarter, and thereafter it was stopped, whereas the TNF inhibitor dose interval was first doubled before reducing the dosage into half, and thereafter it was stopped. The total tapering schedule took 6 months, with dose adjustments every 3 months provided that RA was still well controlled.
Tapering treatment has several benefits, according to the investigators. For the most part, such a strategy reduces the risk of long-term adverse events due to immunosuppression (ie, increased infection risk and possibility of malignancy development). Equally important is the resulting healthcare cost reductions, especially when biologicals are tapered, and a potentially improved compliance. [Best Pract Res Clin Rheumatol 2015;29:550-565;
Ann Rheum Dis 2016;75:45-51]
Conversely, tapering may lead to more transient or persistent disease flares, “which may have a direct impact on patients’ lives (ie, worker productivity and unemployment),” they continued.
The investigators will conduct a follow-up analysis to determine which tapering strategy (complete discontinuation vs dose reduction) for TNF inhibitors is most cost-effective. They explained that the data should help ensure efficient use of biological treatment and, therefore, optimal rheumatic care in the future.
TARA is said to be one of the first trials to assess differences in tapering strategies, as well as to elaborate on current viewpoints concerning tapering treatment, instead of only determining if tapering was feasible or not.
*Tapering strategies in rheumatoid arthritis
**European League against rheumatism