Therapeutics Focus: Psoriasis
Humira Indication Expanded to Include Severe Fingernail Psoriasis
The FDA approved the inclusion of moderate to severe fingernail psoriasis data in AbbVie’s adalimumab (Humira) prescribing information for patients with moderate to severe chronic plaque psoriasis.
The Phase 3 study was dedicated to evaluating fingernail psoriasis in patients with moderate to severe chronic plaque psoriasis. The study demonstrated nearly half of adult patients treated with Humira achieved an assessment of clear or minimal with at least a two-grade improvement from baseline in signs and symptoms of fingernail psoriasis compared to 6.9 percent of placebo patients.
Study: Severe Psoriasis More Common in Men
Severe psoriasis predominantly affects men, according to a new study in the American Journal of Clinical Dermatology.
In the study of 5,438 Swedish psoriasis patients, women had significantly lower median Psoriasis Area Severity Index (PASI) values than men (5.4 for women versus 7.3 for men), and this held across all ages and in all areas of the body except for the head. The study found no differences between women and men in the use of medications before enrolment in the register that would have explained the observed sex difference.
“Our results tell us that the well-established gender differences in the utilization of psoriasis care can at least partially be explained by a higher prevalence of more severe disease in men,” says study author Marcus Schmitt-Egenolf, who is researcher at the Department of Public Health and Clinical Medicine at Umeå University in Sweden. “These findings should motivate a gender perspective in the management of severe psoriasis and its comorbidities, such as cardiovascular and metabolic disease.”
Studies Show Efficacy of Guselkumab
Janssen Research & Development, LLC shared new findings from two pivotal Phase 3 studies. Data from the VOYAGE 2 study showed that patients treated with guselkumab experienced significant improvements in skin clearance and other measures of disease activity compared with placebo, and significantly greater improvements compared with the anti-tumor necrosis factor (TNF)-alpha treatment adalimumab. VOYAGE 2 is the second Phase 3 study to demonstrate superior efficacy of guselkumab versus adalimumab following VOYAGE 1. Data from a third Phase 3 study (NAVIGATE) showed that patients who had an inadequate response following treatment with the anti-interleukin (IL)-12/23 monoclonal antibody (mAb) ustekinumab (Stelara) and who then switched to guselkumab, showed significantly greater improvements in skin clearance compared with patients who continued to receive Stelara. These data were presented at the 2017 American Academy of Dermatology Annual Meeting.
“Guselkumab is a human monoclonal antibody that specifically targets interleukin (IL)-23, a cytokine that plays an important role in the pathogenesis of psoriasis as it is further ‘upstream’ from cytokines like IL-17 and tumor necrosis factor (TNF)-alpha,” Kristian Reich, PhD, MD, Dermatologikum Hamburg, told Practical Dermatology®. “While an investigational treatment, results from the pivotal Phase 3 studies, VOYAGE 1 and VOYAGE 2, showed that treatment with guselkumab resulted in rapid, significant and durable responses over time in patients with moderate to severe plaque psoriasis. Interestingly, guselkumab is also the first IL-23 to demonstrate significant efficacy in the treatment of psoriatic arthritis in a Phase 2 study.” Dr. Reich is also a VOYAGE 2 study investigator.
In the VOYAGE 2 study, the co-primary endpoints were met at week 16, with 84.1 percent of patients receiving guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks achieving an Investigator’s Global Assessment (IGA) score of cleared (0) or minimal (1) disease compared with 8.5 percent of patients receiving placebo. In addition, 70 percent of patients receiving guselkumab achieved a PASI 90 score compared with 2.4 percent of patients receiving placebo.
Major secondary endpoints in VOYAGE 2 achieved statistical significance in comparisons of guselkumab versus adalimumab administered subcutaneously at weeks 0 (80mg), 1 (40mg), and then 40mg every other week (all P < 0.001). At week 16, following three injections of guselkumab and ten injections of adalimumab, significantly higher proportions of patients receiving guselkumab versus adalimumab achieved IGA 0/1 (84.1 percent versus 67.7 percent, respectively) and PASI 90 (70.0 percent versus 46.8 percent, respectively). Guselkumab continued to demonstrate superiority versus adalimumab at week 24 for both the IGA 0/1 and PASI 90 scores. Among other secondary endpoints, significantly higher proportions of patients receiving guselkumab compared with adalimumab achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (indicating no impact of psoriasis on health-related quality of life) and PASI 100 scores at week 24. Additionally, at week 16 and 24, 34.1 percent and 44.2 percent of patients receiving guselkumab achieved PASI 100 responses, respectively.
The NAVIGATE study evaluated the efficacy and safety of guselkumab in patients who continued to experience mild to severe skin symptoms (IGA of 2 or more) following 16 weeks of treatment with Stelara. Patients who switched to guselkumab consistently showed greater improvement in their psoriasis between weeks 28 and 40, compared with patients who continued to receive Stelara, having twice as many office visits with at least a 2-point improvement in IGA from week 16, the study’s primary endpoint, and an IGA score of 0 or 1 (1.5 and 0.7, respectively). Guselkumab also demonstrated superiority across major secondary endpoints in comparisons with Stelara. Major secondary endpoints included the number of visits that patients achieved a PASI 90 response or IGA score of 0 between weeks 28 and 40, and the proportions of patients that achieved an IGA score of 0 or 1 with at least a 2-point improvement from week 16 at week 28. In addition, a significantly higher proportion of patients in the guselkumab group achieved an IGA score of 0 or 1 and at least a 2-point improvement from week 16 at week 52, and a PASI 90 response at weeks 28 and 52, compared with Stelara.
“Pending its approval, guselkumab will offer dermatologists an innovative treatment option for adult patients who may be candidates for biologic therapy, patients who are naïve to such treatments, or who may have not had an optimal response to other regimens previously,” Dr. Reich said. “Certainly as with any medicine or biologic therapy, the safety profile is an important consideration. The benefit-to-risk profile of guselkumab to this point in the clinical development program has been promising, but long-term data will be important to fully understand the safety of guselkumab over time. As guselkumab targets IL-23, one of the targets of Stelara, which targets IL-12 and IL-23, we do have long-term data for that therapy that supports a positive benefit-to-risk profile, which provides a level of confidence for guselkumab as this exciting and potential first-in-class therapy becomes available for patients in the future.”
High Response Rates for Lilly’s Taltz
Patients with moderate-to-severe plaque psoriasis treated with ixekizumab (Taltz, Eli Lilly and Company) demonstrated superior efficacy at 24 weeks compared to patients treated with ustekinumab (Stelara). Detailed results from the IXORA-S study were presented during AAD Annual Meeting.
At 24 weeks, patients treated with Taltz achieved significantly higher response rates compared to patients treated with Stelara, including 83 percent of patients who achieved Psoriasis Area Severity Index (PASI) 90—the study’s primary endpoint—compared to 59 percent of patients who achieved PASI 90 after treatment with Stelara.
In the IXORA-S study, patients were randomized to receive either Stelara (45mg or 90mg weight-based dosing per label) or Taltz (80mg every two weeks for 12 weeks followed by 80mg every four weeks), following a 160mg starting dose, for a total of 52 weeks.
This study also evaluated PASI 75, PASI 100, and static Physician’s Global Assessment score (sPGA) 0 or 1 with at least a two-point improvement from baseline.
At 24 weeks:
• 91.2 percent of patients treated with Taltz achieved PASI 75 vs. 81.9 percent of patients treated with Stelara;
• 83.1 percent of patients treated with Taltz achieved PASI 90 vs. 59.0 percent of patients treated with Stelara;
• 49.3 percent of patients treated with Taltz achieved PASI 100 vs. 23.5 percent of patients treated with Stelara.
Additionally, 86.6 percent of patients treated with Taltz achieved sPGA 0 or 1 compared to 69.3 percent of patients treated with Stelara after 24 weeks.
The majority of treatment-emergent adverse events were mild or moderate. There were no statistically significant differences between treatment groups in overall treatment-emergent adverse events.
Oral Otezla Demonstrates Efficacy
Celgene Corporation shared results from its Phase 4 UNVEIL trial evaluating apremilast (Otezla), an oral, selective inhibitor of phosphodiesterase 4 (PDE4), in patients with moderate plaque psoriasis with a body surface area (BSA) of 5-10 percent, at the AAD Annual Meeting.
The UNVEIL study evaluated the clinical efficacy and safety of oral Otezla 30mg twice daily compared with placebo at week 16 in 221 patients with moderate plaque psoriasis who were naïve to systemic and biologic therapy. At baseline, more than 80 percent of patients enrolled in the trial had previously received topical therapy. The primary endpoint was the mean percentage change from baseline in the product of PGA and BSA (PGA×BSA) at week 16.
At week 16, patients who received Otezla had a significantly greater improvement in mean percentage change from baseline in PGA×BSA compared with those who received placebo (-48.1 vs. -10.2, respectively). In addition, a 75 percent or greater improvement in PGA×BSA score was achieved by 35.1 percent of patients treated with Otezla vs. 12.3 percent of patients treated with placebo. A significantly greater percentage of patients receiving Otezla versus placebo achieved a PGA score of 0 or 1at week 16 (30.4 percent vs. 9.6 percent).
In other secondary endpoints, for enrolled patients who had scalp psoriasis (n=167), a significantly greater percentage who received Otezla achieved a Scalp Physician’s Global Assessment score of 0 or 1 with a greater than two-point reduction from baseline compared with placebo (38 percent vs. 20 percent, respectively).
In a separate pre-specified analysis, patients in UNVEIL reported satisfaction scores based on the Treatment Satisfaction Questionnaire version II that were significantly greater with Otezla than placebo in global satisfaction and effectiveness at week 16. Patients reported no significant difference versus placebo in terms of convenience or side effects.
OTEZLA is not indicated for the treatment of plaque psoriasis patients with BSA involvement of less than 10 percent or sPGA less than 3.