There has been a multitude of publications on Gout at the ACR 2015 Annual Meeting in San Francisco. I’ve select my personal highlights and updates. The second part in on studies concerning drugs to reduce inflammation or to lower uric acid.
Let’s first look at what’s new on febuxostat.
Nicola Dalbeth and colleagues presented: “Imaging and Safety Assessments Following Treatment with Febuxostat and Placebo for 2 Years in Subjects with Early Gout”. Conclusion: “This first clinical trial in early gout subjects demonstrated that treatment with febuxostat can achieve a significant reduction in synovitis compared to placebo.” They didn’t see any difference in the RAMRIS erosion and bone edema scores, which might be due to the fact of having restricted the study to patients with early gout.
Pierre-Antoine Juge and colleagues looked at: “Efficacy and Safety of Febuxostat in 55 Gouty Patients with Stage 4/5 Chronic Kidney Disease: Results from a Retrospective Multicenter Study”. Conclusion: “Febuxostat appears efficient in gouty patients with stage 4/5 CKD or renal transplants. However, safety data is not yet validated with respect to renal function. Further studies with larger samples are warranted for assessing this issue.” That leaves us much at the point, where we’ve been before.
The next study is on arhalofenate, a novel urate lowering anti flare therapy in gout. “It lowers serum uric acid (sUA) by blocking URAT1, a tubular UA transporter, and reduces gout flares by blocking the local release of IL-1β.”
Alexandra Steinberg and colleagues presented: “A Study to Evaluate the Efficacy and Safety of Arhalofenate for Preventing Flares and Reducing Serum Uric Acid in Gout Patients”. “Subjects [N=239] were randomized 1:2:2:2:2 to placebo, arhalofenate 600 mg or 800 mg, allopurinol 300 mg or allopurinol 300 mg combined with colchicine 0.6 mg.“ Conclusion: “Arhalofenate at 800 mg significantly decreases gout flares when compared to allopurinol 300 mg. There was no statistical difference in flares between arhalofenate 800 mg and allopurinol 300 mg combined with colchicine. Arhalofenate 800 mg also significantly decreased flares when compared to placebo. These results indicate that Arhalofenate has intrinsic anti-inflammatory activities clinically associated with improvement in gout flares. Arhalofenate sUA lowering activity, while significant compared to placebo, was lower than in the allopurinol 300 mg groups. Arhalofenate was well tolerated and appeared safe. Arhalofenate is currently in development for the treatment of gout as a combination therapy with ULT, both to lower serum uric acid and prevent flares.” The idea might be to suggest a single therapy for flares and lowering uric acid, and achieving this with a single drug. It looks more like a marketing stunt, no matter how much effect there is on IL-1β. Maybe arhalofenate is aiming at too much at the same time. Just a thought. It’s much too early to evaluate this. Arhalofenate might be useful in the time after the first / a flare.
There were two studies on adding lesinurad either to febuxostat or the allopurinol. I guess, you’re not too surprised that these combinations work.
Let’s close this 2nd part with a study on canakinumab.
Naomi Schlesinger and colleagues presented: “A 3-Year Follow-up Study of Canakinumab in Frequently Flaring Gouty Arthritis Patients, Contraindicated, Intolerant, or Unresponsive to Nonsteroidal Anti-Inflammatory Drugs and/or Colchicine”. The authors looked at patients, who were radomized in the two phase 3 studies (N=456), of these 272 patients were followed up in extension studies, where re-treatment was initiated after a flare. Conclusion: “Over 3 years, a mean “on demand” dosing of CAN was 2.68 per pt. Efficacy of CAN was demonstrated […]”.
I think both flares and urate lowering therapies were addressed in the studies. Gout still is a challenge. I hope that studies will also look at the problem of adherence to drugs.
Dalbeth N, Saag KG, Palmer W, Choi H, Hunt B, MacDonald P, Thienel U, Gunawardhana L. Imaging and Safety Assessments Following Treatment with Febuxostat and Placebo for 2 Years in Subjects with Early Gout [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/imaging-and-safety-assessments-following-treatment-with-febuxostat-and-placebo-for-2-years-in-subjects-with-early-gout/. Accessed November 16, 2015.
Steinberg A, Chera H, Choi YJ, Martin R, McWherter C, Zhang Y, Boudes P. A Study to Evaluate the Efficacy and Safety of Arhalofenate for Preventing Flares and Reducing Serum Uric Acid in Gout Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/a-study-to-evaluate-the-efficacy-and-safety-of-arhalofenate-for-preventing-flares-and-reducing-serum-uric-acid-in-gout-patients/. Accessed November 16, 2015.
Juge PA, Truchetet ME, Ottaviani S, Vigneau C, Loustau C, Cornec D, Pascart T, Cornec-Legall E, Florien M, Bailly F, Schaeverbeke T, Saraux A, Dieude P, Flipo RM, Jean-Baptiste G, Richette P, Lioté F, Bardin T, Chales GH, Ea HK. Efficacy and Safety of Febuxostat in 55 Gouty Patients with Stage 4/5 Chronic Kidney Disease: Results from a Retrospective Multicenter Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-febuxostat-in-55-gouty-patients-with-stage-45-chronic-kidney-disease-results-from-a-retrospective-multicenter-study/. Accessed November 16, 2015.
Saag KG, Bardin T, So A, Khanna P, Storgard C, Baumgartner S, Fung M, Bhakta N, Adler S, Kopicko J, Becker MA. Analysis of Gout Subjects Receiving Lesinurad and Allopurinol Combination Therapy By Baseline Renal Function [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/analysis-of-gout-subjects-receiving-lesinurad-and-allopurinol-combination-therapy-by-baseline-renal-function/. Accessed November 16, 2015.
Dalbeth N, Jones G, Terkeltaub R, Khanna D, Kopicko J, Adler S, Bhakta N, Fung M, Storgard C, Baumgartner S, Perez-Ruiz F. Efficacy and Safety in Patients with Tophaceous Gout Receiving Lesinurad and Febuxostat Combination Therapy: Interim Analysis of an Extension Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-in-patients-with-tophaceous-gout-receiving-lesinurad-and-febuxostat-combination-therapy-interim-analysis-of-an-extension-study/. Accessed November 16, 2015.
Schlesinger N, Bardin T, Bloch M, Lheritier K, Machein U, Junge G, So A, Alten R. A 3-Year Follow-up Study of Canakinumab in Frequently Flaring Gouty Arthritis Patients, Contraindicated, Intolerant, or Unresponsive to Nonsteroidal Anti-Inflammatory Drugs and/or Colchicine [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/a-3-year-follow-up-study-of-canakinumab-in-frequently-flaring-gouty-arthritis-patients-contraindicated-intolerant-or-unresponsive-to-nonsteroidal-anti-inflammatory-drugs-andor-colchicine/. Accessed November 16, 2015.