Benefit–Risk Assessment of Diacerein in the Treatment of Osteoarthritis

Abstract

Osteoarthritis (OA) is the leading musculoskeletal cause of disability. Despite this, there is no consensus on the precise definition of OA and what is the best treatment to improve symptoms and slow disease progression. Current pharmacological treatments include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors. None of those treatments are disease-modifying agents that target the core pathological processes in OA. Diacerein, a semi-synthetic anthraquinone derivative, inhibits the interleukin-1-beta (IL-1β) cytokine which, according to animal studies, plays a key role in the pathogenesis of OA. Diacerein was synthesized in 1980 and licensed in some European Union and Asian countries for up to 20 years. It has shown modest efficacy and acceptable tolerability in a number of trials of low to moderate quality. Early this year, the European Medicines Agency (EMA) conducted a review and restricted the use of diacerein-containing medicines. This was because of major concerns about the frequency and severity of diarrhoea and liver disorders in OA patients. In addition, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) questioned the limited clinical benefits of diacerein, which, in their view, did not outweigh its risks. The aim of this review is to provide a benefit-risk assessment of diacerein in the treatment of OA, based on asystematic evaluation of the published efficacy and safety data. Overall, there is evidence that diacerein is modestly effective for symptoms and possibly for radiographic changes, but this needs to be balanced against higher rates of gastrointestinal toxicity.

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

“…2,3 Consequently, a large portion of unabsorbed DCN remains in the intestine and reaches colon where it is hydrolyzed and converted into rhein (active metabolite of DCN) that possesses local stimulatory effect on the intestinal motility. 3,4 On November 7, 2013, the European Medicines Agency (EMA) restricted the use of DCN-containing medicines because of major concerns about the frequency and severity of diarrhea in OA patients. Furthermore, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) questioned the inadequate clinical benefits of DCN (due to its low bioavailability), which did not offset its risks.…”

From bench to bedside: evolving therapeutic targets in autoimmune blistering disease

“…Diacerein Diacerein is an anthraquinone that modulates expression and activity of interleukin (IL) 1b, a crucial component of the nucleotide-binding domain leucine-rich protein (NLRP) 3-IL-1b-IL-18 axis. 119 Presumably through inhibition of the inflammasome, diacerein also reduced secretion of IL-6 and IL-8 from keratinocyte lines exposed to BP autoantibodies (NCT03286582). Inflammasomes are multi-protein signalling complexes consisting of NLRP3 domains, caspase-1 enzymes and immature forms of IL-1b and IL-18.…”

Dissatisfaction with management of musculoskeletal pain: A global problem and methods of its solution

“…Среди препаратов этого ряда нужно отметить диацереин (Д), обладающий свойствами антагониста ИЛ-1β и способный замедлять раз-рушение суставного хряща и резорбцию субхондральной кости [60][61][62][63]. Эффективность Д как симптоматического и структурно-модифицирующего средства доказана в серии хорошо организованных РКИ и признается многими зару-бежными экспертами [64].…”