Increased insight into the pathogenesis of psoriasis has led to the development of new drugs with novel mechanisms of action, as well as safer and more effective approaches to treatment with conventional drugs
As a result, treatment options for the management of patients with moderate to severe psoriasis in particular – nearly 25% of all patients with psoriasis, according to the National Psoriasis Foundation – have broadened substantially, and research reported during the past year suggests they are on track for continued expansion.
Dr. Craig L. Leonardi
Among the most notable trials of the year were those establishing the "unsurpassed efficacy" of Abbott’s investigational monoclonal antibody briakinumab, according to Dr. Craig Leonardi, a dermatologist and psoriasis specialist at St. Louis University. Like the recently approved psoriatic drug ustekinumab (Stelara), briakinumab is an injectable biologic agent that targets the interleukin-12 and -23 (IL-12/23) proteins, which are believed to promote the inflammation associated with psoriasis.
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IL-12/23 Inhibition
Four phase III clinical studies of briakinumab were presented at the annual meeting of the European Academy of Dermatology and Venereology (EADV) in Gothenburg, Sweden.
– M06-890. In this trial, comparing the efficacy and safety of briakinumab to placebo, 80.7% of the 981 patients randomized to receive briakinumab every 4 weeks following an induction phase experienced a 75% improvement in psoriasis symptoms (PASI 75) at week 12, compared with 4.5% of the 484 patients randomized to placebo. Additionally, 61.6% and 32.2% of patients, respectively, saw 90% and 100% symptom clearance. And at week 52, 82.4% of patients who had achieved PASI 75 maintained at least that level of clearance.
– M10-315 and M10-114. In each of two 12-week trials comparing briakinumab to etanercept, significantly more patients randomized to briakinumab achieved Physician Global Assessment (PGA) scores of 0 or 1 and PASI 75 clearance. In the 350-patient M10-315 and the 347-patient M10-114 studies, respectively, 72.7% and 71% of patients randomized to briakinumab treatment achieved PGA 0 or 1, compared with 29.5% and 39.7% of patients randomized to etanercept therapy and 4.2% and 2.9% of those randomized to placebo.
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Additionally, in the respective studies, 80.6% and 81.9% of the briakinumab-treated patients achieved PASI 75, compared with 39.6% and 56% of the etanercept patents, and 6.9% and 7.4% of the placebo groups.
– M10-255. The fourth trial of 317 patients was a head-to-head comparison with methotrexate in which 81.8% of briakinumab patients achieved PASI 75 clearance at 24 weeks, compared with 39.9% of those taking methotrexate. At 52 weeks, the PASI 75 clearance rates were 66.2% in the briakinumab group and 23.9% in the methotrexate group.
The most common adverse events observed across all four studies and in an ongoing open-label extension were upper respiratory infection, nasopharyngitis, headache, arthralgia, hypertension, and back pain. The incidence of infection and malignancy with briakinumab were higher than those with placebo, but were similar to those in patients treated with etanercept or methotrexate, according to a press release issued by Abbott.
Of particular note is the incidence of major adverse cardiovascular events (MACE) associated with briakinumab, Dr. Leonardi said in an interview. In the M06-890 trial, for example, seven briakinumab patients – all of whom had identifiable underlying cardiovascular risk factors, according to Abbott – experienced a MACE. A similar number of major cardiovascular events were observed in phase III trials of ustekinumab (Stelara), the IL 12/23 antagonist that received Food and Drug Administration approval for psoriasis treatment, he said. "Both drugs share the same mechanism of action, so it’s important to be cautious," he said. "Briakinumab has been submitted for FDA approval. We are awaiting review and comment."
Ustekinumab.
Positive ustekinumab results were also presented last year. A pooled analysis of safety data reported at the summer academy meeting of the American Academy of Dermatology in Chicago demonstrated a favorable risk/benefit profile for up to 3 years of treatment.
Based on integrated data for 3,117 patients from the pivotal phase III PHOENIX 1 and PHOENIX 2 trials and the phase III ACCEPT trial, the investigators reported that the overall rates of adverse and serious adverse events were comparable in the 45-mg and 90-mg ustekinumab patient groups.
For the 45-mg and 90-mg patient groups, respectively, the per-hundred-patient-year rates were 0.82 and 1.50 for serious infections, 0.69 and 0.46 for noncutaneous malignancies, and 0.41 and 0.35 for MACE.
These rates were consistent with expectations for both general and psoriasis populations, and they remained stable over time, according to Dr. Leonardi, one of the study investigators. The maintenance of the favorable safety profile in patients who have been treated for several years is "encouraging," he said, noting that ongoing 5-year follow-up studies will enable continued monitoring of the drug’s safety.