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.
References:
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.
.
No comments:
Post a Comment