During the study, which ran from December 2016 through May 2018, 301 flares were treated: 214 with anakinra and 87 with triamcinolone. Both treatment options reduced pain intensity for both first and subsequent flares.
In an effort to evaluate the efficacy and safety of anakinra compared with triamcinolone for gout flares, investigators discovered that anakinra was comparable in pain reduction and favored for the majority of secondary endpoints. According to a study published in Arthritis and Rheumatology,1 while anakinra was not necessarily better than triamcinolone, it was proven to be an effective alternative option for the treatment of gout flares when conventional therapies were unsuitable due to factors such as comorbidities, intolerance, or are refractory to other therapies.
Generally, patients treat their gout flares with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids. However, comorbidities such as hypertension, kidney and heart disease, and diabetes can impact the way patients are treated. Anakinra works by limiting the activity of IL-1a and IL-18, stopping the binding to the IL-1 type I receptor, which inhibits inflammation and treats gout flares.
“Although anakinra was not superior to triamcinolone, it may be an alternative therapy for patients who cannot tolerate the approved therapies, or who fail to respond to such therapies,” Investigators theorized. “In contrast to glucocorticoids and/or NSAIDs, anakinra has not been reported to exacerbate diabetes, or promote hypertension, renal failure, sodium retention, gastric ulcerogenesis or myocardial infarction. Moreover, colchicine must be dosed with caution in patients with chronic kidney disease, those taking potent CYP3A4 or P-Gp inhibitors, or those on a sustained colchicine flare prophylaxis regimen, or who have recently used colchicine to treat a gout flare.”
Participants in the study (NCT03002974) were eligible if they were diagnosed with gout based on American College of Rheumatology (ACR)/European League Against Rheumatisms 2015 criteria, were unsuitable for both NSAIDs and colchicine, aged ≥18, and had ≥1 self-diagnosed gout flare in the last 12 months. The mean disease duration was 8.7 years and 87% of participants selected were men, 72% were white, with 4.5 self-reported flares.
The randomized, double-blind, double-dummy, active-control study selected 165 patients out of 227 screened (median age 55 years, range 25-83) and treated 110 with anakinra (56 to anakinra 100 mg and 54 to anakinra 200 mg) and 55 with triamcinolone. Patients taking anakinra received either 100 or 200 mg/day for 5 days and those receiving triamcinolone received 40 mg via a single injection in order to ascertain improved patient-assessed pain intensity from baseline to 24-72 hours in the most affected joint measured on a visual analogue scale (0-100). Investigators also assessed secondary outcomes including safety, immunogenicity, and patient/physician global response assessments.
During the study, which ran from December 2016 through May 2018, 301 flares were treated: 214 with anakinra and 87 with triamcinolone. Both treatment options reduced pain intensity for both first and subsequent flares. Median range of study participation was 62.4 weeks for all patients, which was similar for both groups. During the first flare, pain intensity went down -41.2 for anakinra patients and 39.4 for triamcinolone patients (p=0.688). Secondary endpoints favored anakinra and safety findings remained the same. The mean time to pain resolution was 120.5 hours in the anakinra cohort and 167.5 hours in the triamcinolone cohort. Differences in both groups were not significant, however both physician’s and patient’s global response to treatment was significantly better in the anakinra cohort. Emergence of adverse events was similar in both cohorts, with hypertriglyceridemia, neutropenia, and injection sight reactions being the most commonly observed issues.
The study mimicked real-world scenarios that included patients with gout who had aforementioned comorbidities. Limitations included the “ceiling effect” as both medications alleviated gout flare and reduced pain to a similar extent. “Anakinra was not superior to triamcinolone in this study but showed a substantial and similar reduction in patient-assessed pain, and most secondary outcomes favored anakinra,” investigators concluded. “Consistent with current treatment guidelines, anakinra can be considered as an effective option in the treatment of gout flares when conventional therapy is unsuitable.”
Saag KG, Khanna PP, Keenan RT, et al. A randomized, phase 2 study evaluating the efficacy and safety of anakinra in the treatment of gout flares [published online ahead of print, 2021 Feb 18]. Arthritis Rheumatol. 2021;10.1002/art.41699. doi:10.1002/art.41699