Guselkumab may prove to be the treatment option for difficult-to-treat psoriasis

Aug 06, 2018, 12:21pm

For psoriasis in difficult locations including the scalp, palms and soles, guselkumab outperformed adalimumab and placebo, shows a study published online in JAMA Dermatology.

For psoriasis in difficult locations including the scalp, palms and soles, guselkumab outperformed adalimumab and placebo, shows a study published online in JAMA Dermatology.

Historically, said principal investigator Andrew Blauvelt, M.D., M.B.A., of Oregon Medical Research Center, psoriasis of the scalp, nails, palms and soles has proven difficult to clear. "This study shows that guselkumab effectively improves psoriasis in all those areas ― and much more effectively than adalimumab does on the scalp, palms, and soles." The two drugs posted comparable results for nail psoriasis. The study was published online May 16.

Foley et al.'s findings come from a secondary analysis of results from the pivotal VOYAGE one and two trials published in the Journal of the American Academy of Dermatology in March 2017. In these studies, researchers randomized 1,829 patients to receive one of three regimens through week 24:

• Guselkumab 100 mg at weeks zero, four, 12, and 20
• Placebo at weeks zero, four, and 12, followed by guselkumab 100 mg at weeks 16 and 20
• Adalimumab 80 mg at week zero, 40 mg at week one, and 40 mg every two weeks through week 23.

To evaluate drug performance in difficult areas, Blauvelt and colleagues included in their pooled analysis patients with baseline scores of two or higher on scales specific for the scalp (scalp-specific Investigator Global Analysis/ss-IGA; 1,512 patients/82.7 percent), the Physician's Global Assessment of the hands and/or feet (hf-PGA; 461/25.2 percent) and the fingernail PGA (f-PGA; 928/50.7 percent).

For the scalp, palms and soles, guselkumab achieved statistically significantly greater improvements than adalimumab did for near-complete and complete clearance, as well as for complete clearance in these regions, at week 24. For scalp psoriasis, the proportions of patients achieving scores of one or zero (with at least a two-point reduction) in the guselkumab and adalimumab cohorts were 85.0 percent and 68.5 percent, respectively (p<0.001). Likewise, 69.9 percent of guselkumab-treated patients achieved complete scalp clearance, versus 56.3 percent of adalimumab-treated patients (p<0.001), at week 16.

For the palms and/or soles, the proportions of patients in the guselkumab and adalimumab cohorts who achieved week 24 scores of zero or one (with at least a two-point reduction) were 80.4 percent and 60.3 percent (p<0.001). Also at this time point, 75.0 percent and 50.3 percent of patients in these cohorts, respectively, achieved complete clearance (p<0.001).

Regarding fingernail psoriasis at week 24, 60.0 percent and 64.3 percent of guselkumab-treated patients and adalimumab-treated patients, respectively, achieved scores of zero or one (p=0.11). Reasons for this lack of separation between the two treatments are unclear at this time, said Dr. Blauvelt. "It may be that guselkumab takes more time to see a full effect in the nails."

As for strengths of the study's design, he said, "Head-to-head comparative studies are uncommon in dermatology. This represents a large, double-blinded, well-controlled head-to-head trial." Other trials of biologic drugs for psoriasis have rarely looked at hard-to-treat areas as closely as this analysis did, he added.

Study drawbacks include the fact that investigators only reported data out to six months, said Dr. Blauvelt. "We need more long-term data. The VOYAGE 1 and 2 studies have been extended for several years, so these analyses will be forthcoming.”
For now, he said, "Patients can be told that with guselkumab, their traditionally tough-to-clear areas will respond just as well as other areas of the body." It's unclear why psoriasis in these areas has proven so resistant, he said, except that it can take up to a year after successful treatment for healthy looking nails to grow out. It's also difficult for medications to penetrate nails, he added. "In the case of the scalp, palms and soles, one theory is that these areas experience continual trauma from daily activities, which is a known psoriasis trigger (i.e., the Koebner phenomenon)."

As a caveat, he added that the study excluded palmoplantar psoriasis (PPP) – psoriasis which affects only the palms and/or soles, and no other body locations. When patients have plaques on the palms or soles and the body, he said, the palms and soles respond better than when patients have PPP, or exclusively palmoplantar disease.

"We get that question a lot – what do you do for palmoplantar psoriasis? We think of that as a different disease entity compared to people with plaque psoriasis that includes palm and sole involvement." Going forward, said Dr. Blauvelt, it will be important to study whether PPP responds to guselkumab as well as the palms and soles did in the present analysis.

REFERENCE
Peter Foley MD, Kenneth Gordon MD, Christopher EM Griffiths, MD, et al. "Efficacy of Guselkumab Compared with Adalimumab and Placebo in Specific Body Regions: a Secondary Analysis of 2 Randomized Clinical Trials," JAMA Dermatology. May 2018.

DISCLOSURES
Dr. Blauvelt is a scientific advisor and clinical investigator for AbbVie and Janssen, as well as a speaker for Janssen.