Psoriatic arthritis is a type of arthritic inflammation that
occurs in about 15% of patients who have a skin rash called psoriasis, and it
can affect any joint in the body.
Results of a recent clinical trial has revealed that Ixekizumab
not only shows considerable promise for the treatment of moderate to severe
psoriasis, it looks like it may be a winner for comorbid psoriatic arthritis,
too.
According to Dr. Alice B Gottlieb of the Tufts University
School of Medicine, the investigational IgG4 humanized monoclonal antibody
directed against interleukin-17A brought marked improvements in joint pain,
systemic inflammatory burden, and quality of life as well as skin disease in
patients with both psoriasis and self-reported psoriatic arthritis. This result
of a combined analysis of three phase III clinical trials was reported by Dr.
Alice B. Gottlieb at the annual congress of the European Academy of Dermatology
and Venereology in Copenhagen recently.
Details
of the Study
Of the 3,126 patients with moderate to severe psoriasis who
participated in the 12-week trials, 751 (24%) also had self-reported psoriatic
arthritis. Dr. Gottlieb’s analysis focused on them.
She was quick to note that the UNCOVER trials were primarily
psoriasis studies that relied upon patient self-report of psoriatic arthritis.
Nevertheless, it seems likely that the great majority of self-reported
psoriatic arthritis patients really did have the rheumatologic disease, since
the mean baseline C-reactive protein (CRP) level in that group was 8.43 mg/L, a
level far higher than expected in patients with psoriasis only.
In any case, more-rigorous phase III studies of ixekizumab
conducted specifically in patients with formally rheumatologist-diagnosed
psoriatic arthritis and treated in rheumatology practices are due to be
presented at the annual meeting of the American College of Rheumatology in
November 2015. And while Dr. Gottlieb wasn’t at liberty to discuss those results,
she did hint that the data will be strongly positive.
“If you’re happy about these UNCOVER findings, you’ll be
ecstatic about those,” predicted Dr. Gottlieb, professor of dermatology and
dermatologist in chief at Tufts Medical Center, Boston.
Also coming up at the American College of Rheumatology
meeting will be the results of the first-ever head-to-head comparison of an
IL-17 inhibitor versus a tumor necrosis factor–alpha blocker in psoriatic
arthritis patients. While at present most physicians consider a TNF inhibitor
to be the treatment of choice in patients with psoriatic arthritis, that view may change as a result of the
forthcoming comparative study, according to the dermatologist.
In each of the three phase III UNCOVER studies, patients
were randomized to 12 weeks of subcutaneous ixekizumab at 80 mg every 2 or 4
weeks following a 160-mg loading dose, or to placebo. At baseline, the subgroup
with self-reported psoriatic arthritis had a mean Psoriasis Area and Severity
Index ( PASI) 0f about 21, a self-rated joint pain severity of 50 on a 0-100
scale, a CRP of 8.43 mg/L, and a Dermatology Life Quality Index (DLQI) score of
14.
The
Results
Joint pain decreased dramatically in the two ixekizumab
groups as early at 2 weeks into the trial, at which point, patients on
treatment every 2 weeks averaged a 13.1-point reduction from baseline, with a
similar 14.1-point drop noted in those on an every 4 weeks schedule. At week
12, the mean reductions from baseline were 25.2 and 26.8 points, compared with
a 1.1-point increase in joint pain among placebo-treated controls.
Inflammatory burden plunged quickly, as evidenced by mean
reductions in CRP of 4.63 mg/L and 4.33 mg/L at week 1 with biweekly and
monthly dosing, respectively. These reductions were then maintained through
week 12.
In terms of improvement in skin symptoms, with ixekizumab
dosed every 2 weeks, the PASI 75 response was 89.8% at 12 weeks, the PASI 90
response was 69.3%, and the PASI 100 response (clear skin) was 37.1%. In
patients treated every 4 weeks, the rates were 81.1%, 60.8%, and 34.7%.
“There’s good news in both groups, but I think the news is
even better in the every-2-weeks group,” Dr. Gottlieb commented.
The ixekizumab-treated groups also showed what Dr. Gottlieb
described as “dramatic” improvements – in the 4+ to 5+ point range – in both
the mental and physical component scores on the SF-36, another widely used
quality of life measure.
Improvements in skin and self-reported joint symptoms
appeared to correlate. “Obviously, one needs to look at this more carefully in
a phase III psoriatic arthritis study. That’ll provide a more robust answer.
But this gives a hint,” she said.
The UNCOVER program was sponsored by Eli Lilly. Dr. Gottlieb
serves as an adviser to Lilly and numerous other pharmaceutical companies.
#PsoriaticArthritis #JoinPain #Inflammation #Arthritis
