Effect of Ixekizumab on Patient Reported Outcomes and Quality of Life in Patients With Moderate-to-Severe Plaque Psoriasis: 5-Year Results from the UNCOVER-1 and -2 Studies

This study shows that ixekizumab treatment resulted in improvements in the PROs of itch and skin pain, health-related QoL, bothersomeness of skin disease, and work productivity in patients with moderate-to-severe plaque psoriasis that were sustained from 60 to 264 weeks of treatment in the UNCOVER-1 and -2 studies. Although these studies were not designed to compare the ixekizumab study arms across the 2 studies, they appeared to result in similar health outcome results at week 264. The baseline characteristics and disease characteristics of the long-term extension population were similar to that of overall population previously reported.^9,11 The patient baseline mean PASI score and skin pain VAS were indicative of high disease severity at study enrollment, and the SF-36 MCS and SF-36 PCS suggested psoriasis was having a moderate impact on patients’ health-related QoL.

Ixekizumab treatment also resulted in improved DLQI and SF-36 measures at 264 weeks in both the UNCOVER-1 and -2 studies. Improvement related to skin symptoms was demonstrated by PROs as measured by the itch NRS and DLQI scores. Ixekizumab treatment resulted in improved DLQI scores, with over three quarters of patients reporting that their psoriasis-associated skin symptoms had no effect on their lives (DLQI 0,1). These findings have substantial implications for patients with moderate-tosevere psoriasis since improvements in the severity of skin disease have been shown to be associated with enhanced health-related QoL.^14-16

The personal and economic burden of psoriasis is considerable. Impaired physical function and work difficulties are associated with psoriatic skin disease, whereas severity of the skin disease is associated with poor mental functioning.¹⁷ A nationwide, cross sectional study of patients in the US with moderate tosevere psoriasis showed that biologic therapy was associated with significantly greater increases in measures of physical and mental functioning compared with oral therapy.¹⁸ In the UNCOVER-1, -2, and -3 studies, patients treated with ixekizumab reported statistically significant improvements in mean SF-36 PCS and SF-36 at 12 weeks that persisted through week 60.¹⁹ Here, we build on these findings and show that patients treated with ixekizumab reported improvements in skin disease, with improvements in health-related QoL measured by the DLQI and SF-36 as well as the individual domain scores, that were maintained through 264 weeks of treatment.

There are also indirect costs for people with psoriasis, including disability (short- and long-term) and lost productivity through an inability to undertake paid and unpaid work.¹⁷ In our study, patients treated with ixekizumab reported sustained work productivity measured by reduced presenteeism (reduced/ impaired effectiveness at work), work productivity loss (overall work impairment associated with absenteeism and presenteeism), and activity impairment (activities performed outside of work) at week 264.

The main limitation of this study was that the active comparator, etanercept, was only evaluated up to 12 weeks and the longterm treatment period was open-label. The strength of this study is that the inclusion criteria reflect most patients affected with moderate-to-severe plaque psoriasis, making the results generalizable to a large population. In addition, the efficacy results were validated through replication in 2 independent studies.

Ixekizumab provided clinically meaningful and sustained improvements in itch, skin pain, QoL, PSAB, SF-36 MCS, and SF- 36 PCS through 5 years of continuous treatment in patients with moderate-to-severe plaque psoriasis.

Melinda Gooderham has been an investigator, speaker, and/ or advisor for AbbVie, Amgen, Akros, Arcutis, Boehringer Ingelheim, BMS, Celgene, Dermira, Dermvant, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, UCB, and Bausch/Valeant. Boni Elewski served as a consultant receiving honoraria for Arcutis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly and Company, LEO Pharma, Menlo, Novartis, Pfizer, Sun Pharma, UCB, Valeant, and Verrica, and received clinical research support funding to her university from AbbVie, AnaptysBio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Incyte, LEO Pharma, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, Valeant, and Vanda. Matthias Augustin has served as a consultant or paid speaker for AbbVie, Almirall, Amgen, Beiersdorf, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly and Company, Galderma, GlaxoSmithKline, Janssen- Cilag, LEO Pharma, Medac, Merck, Merck Sharp & Dohme, Novartis, Pierre-Fabre, Pfizer, Sanofi, Trevi, UCB, and XenoPort. Lars Iversen has been an investigator, paid speaker, consultant, and advisory board member for AbbVie, Eli Lilly and Company, Janssen-Cilag, LEO Pharma, Merck Sharp & Dohme, Novartis, and Pfizer; has been a paid speaker, consultant, and advisory board member for Almirall; has been an investigator for Amgen; has been an advisory board member for UCB; and has received research and educational grants from AbbVie, LEO Pharma, Merck Sharp & Dohme, Novartis, and Pfizer. Hideshi Torii has received consulting fees or honoraria from AbbVie, Celgene, Eli Lilly and Company, Janssen, Kyowa Hakko Kirin, Mitsubishi Tanabe Pharma, and Novartis. Russel Burge, Kyoungah See, Gaia Gallo, and William J Eastman are full time employees of, and own stock in, Eli Lilly and Company. Missy McKean-Matthews is a full time employee of Syneos Health.