UNCOVER-2 Analyses Provide Additional Treatment Insights

Treatment of psoriasis with a second biologic was effective even in patients who did not respond to a first biologic, according to results of a new analysis from the UNCOVER-2 study. Another analysis from this study showed that ixekizumab, a humanized, high-affinity monoclonal antibody against the proinflammatory cytokine interleukin (IL)-17A, yielded greater improvements than etanercept or placebo for the treatment of palmoplantar plaque psoriasis. The analyses were presented at AAD 2016.

The UNCOVER-2 study in 1,224 patients with moderate-to-severe plaque psoriasis, defined as a psoriasis area severity index (PASI) ≥12, a static physician global assessment (sPGA) ≥3, and involvement of ≥10% of the body surface area (BSA), evaluated two different doses of ixekizumab (80 mg every 4 weeks and 80 mg every 2 week, after a 160 mg starting dose), etanercept 50 mg twice weekly, and placebo. After the 12-week induction period, both doses of ixekizumab were associated with greater improvements in PASI 75 and sPGA responses, compared with etanercept and placebo [Griffiths CE et al. Lancet 2015].

Following study protocol, patients who did not achieve an sPGA score of 0 or 1 with etanercept at Week 12 (ETN nonresponders) were switched to ixekizumab 80 mg every 4 weeks, starting at Week 16 after a placebo washout, and the placebo patients were switched to ixekizumab 80 mg every 4 weeks starting at Week 12. The results of this analysis were presented by Kim Papp, Probity Medical Research, Waterloo, Canada, who noted there had been clinical observations that suggested the efficacy of a biologic could be affected by previous treatment with another biologic.

The patients in the ETN nonresponder (n=200) and placebo (n=155) groups were similar at baseline. Their mean age was 45 years and most were white (70%). Their mean duration of psoriasis was 19 years, BSA 27%, sPGA 3.5, and PASI 20.

The proportion of patients in the ETN nonresponder and placebo groups achieving an sPGA 0/1 score, PASI 75, PASI 90, and PASI 100 response at Week 12 and Week 60 with ixekizumab treatment is detailed in Table 1.

The PASI 100 response achieved at 12 weeks in the placebo group was maintained through 60 weeks, while in the ETN nonresponder group there was an increase from 12 weeks to 60 weeks in the PASI 100 response. The dermatology life quality index (DLQI) improved in the ETN nonresponder group with ixekizumab treatment, with 58% of patients achieving a DLQI 0/1 at week 60, compared with 46.0% at week 12. In the placebo group, the proportion was similar at week 60 and 12 (63.9% and 60.0%, respectively).

The safety profile was similar in the ETN nonresponder and placebo groups, with no meaningful difference between the populations, stated Dr. Papp. Treatment-emergent adverse events (AEs) occurred in 79% of the ETN nonresponder group and 80.6% of the placebo group; 8 patients in each group discontinued treatment because of a serious AE. The most frequent AE was injection site reaction. One patient in the placebo group had a nonfatal myocardial infarction and one patient in the ETN nonresponder group had a nonfatal stroke.

Overall, this analysis demonstrated that the response rates and safety profile at Week 60 were similar in patients previously treated with placebo or etanercept and switched to treatment with ixekizumab 80 mg every 4 weeks.

Prof. Kristian Reich, MD, Dermatologikum Hamburg, Germany, presented the results in the 105 patients with moderate-to-severe palmoplantar psoriasis (PPASI ≥8 at baseline). Their mean PPASI score was 19.39 at baseline, and all had classical palmoplantar psoriasis.

The PPASI 75 and PPASI 100 responses in this population at Week 12 were similar to the PASI 75 and 100 responses in the overall UNCOVER-2 population (Table 2).

The mean change in the PPASI score from baseline to Week 12 was –4.6 with placebo, –12.2 with etanercept, –17.0 with ixekizumab 80 mg every 4 weeks

There were greater reductions in the mean change in the PPASI score from baseline to Week 12 with ixekizumab 80 mg every 4 weeks (–17.0) and ixekizumab 80 mg every 2 weeks (–17.0), compared with placebo and etanercept (–4.6 and –12.2, respectively). The mean percent improvement in PPASI at Week 12, an indicator of the pharmacokinetics of the drug, was also greater with ixekizumab (89.9% and 88.31% with the every 4 and 2 week regimens, respectively), versus placebo and etanercept (16.3% and 64.3%, respectively).

These results provide reassurance that patients with all manifestations of psoriasis received benefit with ixekizumab treatment, stated Prof. Reich. Further study in larger populations with various forms of palmoplantar psoriasis are needed to better understand the effect of treatment with ixekizumab.