Combination Therapies of Diacerein and Febuxostat Inhibit IL-1β Responses and Improve Clinical Symptoms in Patients With Refractory Gout

Abstract

There are several therapeutic strategies available for the treatment of an acute gout attack and the prevention of recurrent gout flares, and they include nonsteroid anti-inflammatory drugs. This prospective study was aimed at evaluating the efficiency and safety of diacerein in combination with febuxostat on urate control, global assessments of disease activity, self-monitored gouty acute flare times, inflammatory markers, and clinical symptoms associated with their life quantity in patients with refractory gout. A total of 64 patients with refractory gout were sequentially recruited and prescribed with oral febuxostat alone or febuxostat plus diacerein daily for 12 weeks. The intensity of joint pain, numbers of acute flare, disease activity and the levels of serum amyloid A, mature IL-1β, IL-18, C-reactive protein, and urate in individual subjects were routine analyzed. In comparison with that treatment with febuxostat alone, treatment with both drugs for 12 weeks had a better therapeutic effect on reducing the values of visual analog scales, acute flares, and healthy assessment questionnaire scores in these gout patients. Furthermore, treatment with both drugs also significantly reduced the mean daily dose of etoricoxib and the levels of serum IL-1β and serum amyloid A. There was no significant difference in the frequency of patients with adverse effect between these 2 groups of patients. In conclusion, combination of diacerein and febuxostat had better therapeutic effect on reducing acute gout flares, inflammation, and clinical symptoms in patients with refractory gout.

Comparison of the therapeutic effects of febuxostat combined with a low‐purine diet and allopurinol combined with a low‐purine diet on the improvement of gout patients

“…The occurrence of gout can bring severe pain to patients. If effective treatment measures are not taken, the acute attacks of gout in patients are more frequent, which is the main factor that reduces the quality of life of patients 27 . Maekawa et al 28 .…”

“…26 The results of this study showed that after 6 months of treatment, the levels of TNF-a, IL-1β, and IL-18 in the study group were lower than those If effective treatment measures are not taken, the acute attacks of gout in patients are more frequent, which is the main factor that reduces the quality of life of patients. 27 Maekawa et al 28 suggested that non-bisphosphonate combined with allopurinol can relieve pain and have significant therapeutic effects in patients with refractory gout. The results of this study showed that after 6 months of treatment, the degree of pain in the study group was lower than that in the control group (p < .05), suggesting that non-bisphosphonate combined with a low-purine diet can effectively alleviate the degree of pain in gout patients.…”

Novel inhibitory effects of dotinurad, a selective urate reabsorption inhibitor, on urate crystal-induced activation of NLRP3 inflammasomes in macrophages

“…The benefits of dotinurad as an SURI, which inhibits NLRP3 inflammasomes and URAT1, are evident. Several non-SURIs have been reported to inhibit NLRP3 inflammasomes 23,24,28) , including benzbromarone, which is commercially available ( Figures 5, 6 and 7). However, benzbromarone also strongly inhibits ABCG2 16) , which plays a role as a gatekeeper against xenobiotics and regulates pharmacokinetics and efficacy of substrate drugs for ABCG2.…”

“…Urate-lowering anti-flare therapy aims to reduce both serum uric acid levels and gout flares by uricosuric action and the blocking of urate crystal-stimulated release of IL-1β from neutrophils or macrophages, respectively 23,24) . In the present study, we investigated the effects of dotinurad, an SURI, on the stimulation of NLRP3 inflammasomes by MSU crystals in LPS-primed mouse J774 macrophages, which ultimately suggested that this drug can inhibit the MSU crystal-stimulated IL-1β release from macrophages by activating NLRP3 inflammasomes.…”