Followup Data Validate New PsA Drug Apremilast

November 24, 2014

(ACR2014) Hot news at last year's American College of Rheumatology annual meeting, the newly approved psoriatic arthritis drug apremilast has proven safe and effective in longer-term studies.

Mease PJ, Adebajo AO, Gladman D, et al. Long-term (104-Week) Safety Profile of Apremilast, an Oral Phosphodiesterase 4 (PDE4) Inhibitor, in Patients with Psoriatic Arthritis: Results from a Phase 3, Randomized, Controlled Trial and Open-Label Extension (PALACE1). Abstract #1564. Arthritis & Rheumatism. 2014. 66(1) Supplement.

Schafer P, Chen P, Fang L, Wang A, Chopra R. Psoriatic Arthritis: Pharmacodynamic Results of a Phase 3, Randomized, Controlled Trial. ACR  Abstract # 955, Arthritis & Rheumatism. 2014. 66(1) Supplement.

The newly approved PDE4 inhibitor apremilast (Otezla), whose Phase III results for psoriatic arthritis were probably the hottest news at last year's American College of Rheumatology (ACR) annual meeting, has now stood up to longer-term scrutiny in studies. After two years of followup, the drug appears not only effective but safe for psoriatic arthritis (PsA).

More than a half-dozen poster presentations at the 2014 meeting of the ACR in Boston reported improvements in enthesitis, dactylitis, function, pain, and fatigue in PsA patients in late-stage clinical trials-as well as favorable comparisons with adalimumab (Humira) and methotrexate (MTX).

The 104-week safety data from an open-label extension of the phase 3 Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE1) trial show twice-daily 20mg and 30mg apremilast continue to be well-tolerated with no new safety concerns, according to a poster presentation coauthored by Philip J. Mease MD, director of rheumatology research at the Swedish Medical Center in Seattle and a clinical professor of medicine at the University of Washington (first citation above).

The study shows no increase in the incidence and severity of adverse events with long-term exposure.

Pharmacodynamic data from PALACE1 reported at an ACR clinical session reveals that apremilast not only acts against PDE4 but also decreases tumor necrosis factor alpha (TNFα) and other inflammatory cytokines.

“At week 4, the earliest time-point measured, there was a 60% increase in TNFα in the placebo-treated group. In the two apremilast-treated groups there was a dose-dependent decrease in TNFα,” says Peter H. Schafer PhD, a researcher for Translational Development at Celgene Corporation, Otezla’s manufacturer. “This suggests that apremilast acts, at least in part, by controlling the over-expression of TNFα.”

In fact, TNFα fell by 40% in the 20 mg group at 4 and 16 weeks.

The industry-sponsored pharmacodynamic analysis of peripheral plasma samples from 150 PALACE1 participants also shows significant decreases in the chemokines interleukin 8 (IL-8) and MIP-1βl.

There were also significant drops by week 40 in IL-6 and in the cytokines IL-17 and IL-23, two key players in the development of PsA. This is the first time such effects have been observed.

This translates into clinical improvements in PsA patients, seen in ACR20 responses at both doses of the drug.

“ACR20 responses were just above 50% and those clinical responses were sustained throughout that two-year period of continuous treatment with apremilast,” Schafer told the audience.

Schafer and colleagues plan to continue their analyses in an ongoing PsA clinical trial.