Selection of strategy for high-risk early RA remission induction hinges on safety

MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.

The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.

^{Sara Freeman/Frontline Medical News}

Veerle Stouten

Ms. Stouten added that, according to international guidelines, achieving clinical remission means treating patients early, as soon as possible after the diagnosis of rheumatoid arthritis is made; intensively, with a DMARD, preferably methotrexate if not contraindicated, combined with short-term glucocorticoids; and to target, meaning treatment should be targeted at achieving remission or at least low disease activity in every patient.

The CareRA trial was a prospective, randomized, multicenter trial set up to see which of three methotrexate-based, steroid-containing intensive regimens would be best for inducing remission in patients with high-risk RA. The pragmatic trial was conducted in 13 Belgian rheumatology practices recruiting 400 patients, 300 of whom were designated as high risk for progression based on factors such as their antibody status and presence of joint erosions. CareRA trial investigators defined clinical remission as less than 2.6 on the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP).

The three regimens all contained a weekly 15-mg dose of methotrexate and prednisone 30 mg or 60 mg that was then tapered weekly after the first 6-7 weeks.

In the COBRA Classic regimen, methotrexate was partnered with sulfasalazine, given as a 2-g daily dose. Prednisone was initially given at a dose of 60 mg and then taped to 5.7 mg starting at week 7.

For the COBRA Slim regimen, just methotrexate and prednisone were used, with the latter started at a dose of 30 mg and then tapered to 5 mg starting at week 6.

Lastly, the COBRA Avant-Garde regimen saw methotrexate combined with leflunomide, 10 mg daily, and the same step-down prednisone regimen as COBRA Slim.

In the first year, treatment in each group was adjusted to achieve a target of low disease activity (DAS28-CRP of 3.2 or lower), with measurements taken every 3 months. The steroid component was stepped down further after 28 weeks and stopped altogether by 34 weeks. The aim was also to reduce the number of DMARDs used, such that everyone was on DMARD monotherapy if possible. In the second year, rheumatologists could treat patients at their own discretion, with adjustments to treatment made according to DAS28-CRP at visits every 3 months.

Ms. Stouten reported that all three of the intensive induction regimens “were very effective in our high-risk population and that they showed persistently high remission rates at year 2.”

The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 65.3% for the COBRA Classic regimen, 73.5% for COBRA Slim, and 73.1% for COBRA Avant-Garde.

For inducing remission, however, she suggested that the COBRA Slim regimen might have the edge from a benefit-to-risk perspective.

A total of 60.2% of COBRA Slim patients were in remission at year 1, and 67.8% of them remained in remission throughout year 2. Also, fewer COBRA Slim patients needed biologic therapy, both overall (n = 11) and in the first year (n = 2), when compared with the other two regimens. However, in the COBRA Classic arm, 65.3% were in remission at year 1, and 54.7% of those patients maintained it throughout year 2, whereas in the COBRA Avant-Garde arm the rates were 61.3% at year 1, with 70.2% of those maintaining remission throughout year 2. A total of 18 patients in the COBRA Classic group started biologics, including 10 in the first year, compared with 15 in the COBRA Avant-Garde group, 7 of those in the first year.

“For maintaining remission, there were no statistically significant differences observed in remission rates at year 2 between treatment groups,” Ms. Stouten observed. “However, COBRA Avant-Garde had numerically better CDAI [clinical disease activity index] remission rates at year 2 [48.2% vs. 33.7% for COBRA Slim and 34.7% for COBRA Classic; P = .068].”

The total numbers of patients reporting adverse events related to treatment were lower with the COBRA Slim regimen (n = 164) than with COBRA Classic (n = 209) and COBRA Avant-Garde (n = 208). Fewer COBRA Slim patients also had to stop treatment (5 vs. 9 with COBRA Classic and 12 with COBRA Avant-Garde) or have interrupted treatment (12 vs. 17 and 19, respectively) because of adverse events.

Ms. Stouten had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).

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