EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
WAIKOLOA, HAWAII (FRONTLINE MEDICAL NEWS) – Scrutiny of the number needed to treat with various systemic drugs to achieve a Psoriasis Area and Severity Index–90 (PASI-90) response in psoriasis highlights the folly of current stepwise treatment strategies imposed upon dermatologists by many payers, Dr. Craig L. Leonardi asserted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“It’s time to rethink our goals,” declared Dr. Leonardi, a dermatologist at Saint Louis University and a noted clinical trialist.
Most health plans insist that patients with moderate to severe psoriasis must have tried methotrexate and failed to achieve an adequate response before moving on to costlier biologic agents. But a PASI-90 response rate, indicative of 90% improvement in psoriasis area and severity, was achieved in only 13.6% of patients on methotrexate in the CHAMPION trial, compared with 59.2% and 70.9% of patients in phase III randomized trials of the interleukin-17 antagonists secukinumab (Cosentyx) and ixekizumab, respectively.
In other words, it is now routinely possible using highly effective medications to achieve a PASI-90 response in the majority of psoriasis patients, he noted.
Although statisticians say it isn’t appropriate to compare outcomes across clinical trials because study populations may differ, Dr. Leonardi decided it nevertheless would be illuminating to compare NNTs (the number of patients who needed to be treated with a medication instead of placebo to achieve one additional responder in a defined time period). In this analysis, he used data from phase III randomized, placebo-controlled clinical trials and Food and Drug Administration–regulated package inserts to calculate NNTs for systemic medications for psoriasis for the 10- to 16-week duration of phase III trials. The NNTs for a PASI-90 response ranged from a whopping 43.5 for methotrexate to 1.7 with secukinumab and 1.4 for ixekizumab.
“You can see immediately that methotrexate is outed as a weak and ineffective drug. And yet which drug are we usually asked to use first? Methotrexate. This is a structural problem that we have to solve in our specialty. We have to get with the insurance industry, we have to get with our guidelines of care and rewrite them. There is no reason that this drug should be placed in front of any of the other drugs, which are much more effective,” Dr. Leonardi said.
Viewing the data another way, the proportion of patients who achieved a PASI-75 response at the time of a major placebo-controlled clinical trial’s primary endpoint ranged from a low of 35.5% with methotrexate to 81.6% with secukinumab and 89.1% with ixekizumab. The NNTs to get a PASI-75 improvement with secukinumab and ixekizumab were, respectively, 1.3 and 1.2, compared to 6.0 for methotrexate.
“With an NNT of 1.2, if you treat 12 patients with ixekizumab, 10 of them are going to achieve PASI-75. This is a very different world than we had at the beginning of this adventure back in the early 2000s,” he observed.
In the modern era of highly effective biologic therapies for psoriasis, it makes sense to push as hard as possible in an effort to try to clear patients, according to Dr. Leonardi. That’s in part because the closer patients come to that once-nearly-unattainable goal, the better they actually feel, as underscored in the phase III results for ixekizumab.
In that study, the proportion of patients with a Dermatology Life Quality Index ( DLQI ) score of 0 or 1 at week 12 rose stepwise with the size of their PASI response. Among patients with a week-12 PASI response of 50 to less than 75, 18.8% had a DLQI of 0 or 1. For patients with a PASI-75 to less than PASI-90, it jumped to 52.3%. Among subjects with a PASI-90 to less than 100, 66.9% had a DLQI of 0 or 1. And among the 35.3% of ixekizumab-treated patients who had a PASI-100 response, the likelihood of a DLQI of 0 or 1 rose to 71.1%.
Noting that etanercept (Enbrel) is the only biologic on the market that achieves a PASI-75 response in less than half of treated patients, Dr. Leonardi said, “I’m over using etanercept as a first-line biologic. It’s the weakest biologic we can pick right now. I really like the highly efficacious drugs. I like adalimumab. I like the efficacy I see with ustekinumab. I like secukinumab. They are all preferred first-line drugs if I can get them, but it’s an insurance company world. I can’t tell you how many times I’ve heard, ‘Well, we’re not saying you can’t prescribe it, Dr. Leonardi, we’re just not going to pay for it.’ ”
Ixekizumab is under FDA review for psoriasis and a decision is expected within the first quarter of 2016, according to a spokesperson for Eli Lilly.
Dr. Leonardi is a recipient of research grants from well over a dozen pharmaceutical companies and is a consultant to and/or member of the speakers bureaus for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Janssen, Eli Lilly, Leo, Novartis, Pfizer, Sandoz, UCB, and Vitae.
SDEF and this news organization are owned by the same parent company.