Adverse events related to Diacerein are less common than expected in a specialized rheumatology center

Abstract

Purpose: Osteoarthritis (OA) is one of the most prevalent musculoskeletal conditions. One of the emergent but controversial OA treatments due to adverse gastrointestinal events is the Diacerein; this is an anthraquinone that interferes with interleukin-1, a cytokine involved in the destruction of cartilage and inflammation, which plays a role in the development of structural damage as well as symptoms in OA. A Cochrane review showed that the most frequent adverse event with this medication is diarrhea compared to placebo RR 3.52 (95% CI 2.42 to 5.11) or other symptomatic slow acting drugs for OA RR 3.20 (95% CI 1.58 to 6.49). The aim of this study is to describe demographic data and adverse events (AE) in a group of patients taking Diacerein for OA in a specialized rheumatology center in Colombia. Methods: We performed a descriptive cross sectional study. We included patients with confirmed diagnosis of OA alone or in coexistence with rheumatoid arthritis (RA). Patients were followed during a 12 month period for AE. Adverse events were classified according CTCAE to the Common Terminology Criteria for Adverse Events. Descriptive epidemiology for continuous variables, measure of central tendency and dispersion for qualitative and categorical variables through percentages and averages were calculated; we analyzed some bi-variated correlations with X2 test. Results: We included 360 patients 61% (220) with diagnosis of osteoarthritis alone and 39% (140) with OA in coexistence with rheumatoid arthritis. The mean age was 69.4 ± 6.7 years; most of patients were between 60 and 80 years old, 86% were women. From the total of patients 91% were polymedicated (received more than three drugs) and were taking 100 mg of Diacerein daily. During the 12 month follow-up period there were 37 adverse events (in 10.2% of patients), 25 in the group with OA alone and 12 in the group with OA in coexistence with RA. The most common adverse event was dyspepsia (13/37 - 3.6% of patients), followed by diarrhea (10/37 - 2.8% of patients), nausea (5/37 - 1.4% of patients), epigastric pain (3/37 - 0.8% of patients), abdominal pain (2/37 - 0.5% of patients), elevated alanine aminotransferase (2/37 - 0.5% of patients), dysuria (1/37 - 0.3% of patients) and tachycardia (1/37 - 0.3% of patients). According to the CTCAE to the Common Terminology Criteria for Adverse Events classification most of these adverse events were mild 95% and 5% severe; and predominantly gastrointestinal AE. There were no statistical correlation between age groups or polymedicated groups and adverse events; there were no statistical differences between OA alone and OA plus RA treatment groups; surprisingly nobody reported changes in urine coloration, an AE that is very common in other reports. Conclusions: Gastrointestinal adverse events were observed mainly, but in a small portion of the patients. Diarrhea was not present as previously described in the literature. On the other hand, it is noteworthy that even in those patients who were taking medications concomitantly for rheumatoid arthritis there was no increase in the frequency of adverse events. For this reason Diacerein can be considered a safe medication for the treatment of OA. Obviously, it is necessary to carry out more long-term follow-up studies to evaluate the safety and effectiveness of the Diacerein.