Diacerein may be a safe and efficacious treatment option in patients with rheumatoid arthritis (RA) who are inadequate responders to methotrexate (MTX) therapy, according to preliminary results from a pilot study published in Clinical Rheumatology.

Researchers conducted a pilot, multicenter, double-blind, placebo-controlled trial of patients with RA who were inadequate responders to MTX therapy (ClinicalTrials.gov Identifier: NCT01264211).

Patients (N=40) were randomly assigned to receive either diacerein or a placebo as an add-on to MTX therapy for 24 weeks. Ultimately, 16 and 19 patients in each group completed the study, respectively. The primary efficacy endpoint was the percentage of patients who attained 20% improvement according to American College of Rheumatology response criteria (ACR20) at 24 weeks; the secondary efficacy endpoint was the percentage of patients who achieved at least a moderate response according to European League Against Rheumatism criteria and the change in the  Disease Activity Score of 28 joints calculated using the erythrocyte sedimentation rate (DAS28-ESR) at 24 weeks. Safety endpoints included incidence, type, and intensity of adverse events (AEs) and general changes in vital signs or laboratory values.

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At baseline, patient characteristics in both treatment and placebo arms were comparable, with the exception of tender joint count (16.6 ± 9.3 vs 23.2 ± 9.6), DAS28-ESR (6.2 ± 0.7 vs 6.8 ± 0.8), and proportion of patients taking nonsteroid anti-inflammatory drugs (70% vs 95%), which were all elevated in the placebo arm.

Among patients in the diacerein group, the percentage of patients who achieved ACR20 continued to increase until week 24; this increase was slower and inconsistent in the placebo group. By week 4, the differences in ACR20 between the two groups was significant (25% diacerein; 0% placebo); however, by the primary endpoint at week 24, this response was no longer significant (65% diacerein and 45% placebo).

Investigators performed a multivariate logistic regression to further examine ACR20. These results indicated that the odds of response to treatment were 2 times higher in the diacerein group vs the placebo group (odds ratio [OR] 2.27; 95% CI, 0.64-8.11; P =.21). After adjustment for baseline tender joint count and DAS28-ESR, diacerein therapy was still associated with higher ACR20, although this response was not statistically significant (OR 3.12; 95% CI, 0.66-14.69; P =.15).

In the diacerein group, a significantly higher percentage of patients achieved a moderate European League Against Rheumatism response at week 24 (75% vs 25% placebo, P =.002). No significant difference in change in DAS28-ESR was noted from baseline to week 24 (intergroup difference 0.41; 95% CI, −0.4 to 1.23); 50% improvement in American College of Rheumatology response criteria was higher at week 24 in the diacerein group (40%; 95% CI, 11%-50%), but 70% improvement according to American College of Rheumatology criteria was identical in both groups (5%; 95% CI, −6% to 16%).

The percentage of patients reporting treatment-emergent AEs were similar in both groups (80% in diacerein and 75% in placebo), and only 2 patients (1 in each group) experienced a serious AE. Neither serious AE was considered related to the study treatment.

The primary limitation of the study was the small sample size, which was arbitrarily fixed at 20 patients per treatment arm. Because this was a pilot study, “the optimal dosage and the appropriate duration of diacerein treatment to have an effect on the clinical symptoms of RA were not known,” cautioned researchers.

“This pilot study showed the potential benefits of using diacerein in the treatment of [patients with RA] with insufficient response to MTX,” the researchers concluded. “The learnings of this pilot study in patients with RA should allow designing larger trials, with longer treatment duration and possibly higher drug doses, to further evaluate the efficacy of diacerein not only on the symptoms of RA but also its effect on joint structures.”

Drs Loutherenoo and Siripaitoon reported receiving speaking honoraria from TRB Chemedica (Thailand) Ltd. Dr Basset is an employee of TRB Chemedica International SA, Geneva, Switzerland.

Reference

Louthrenoo W, Nilganuwong S, Nanagara R, Siripaitoon B, Basset SC. Diacerin for the treatment of rheumatoid arthritis in patients with inadequate response to methotrexate: a pilot randomized, double-blind, placebo-controlled add-on trial [published online May 19, 2019]. Clin Rheumatol. doi:10.1007/s10067-019-04587-1