At the 2023 Annual Meeting of the American Academy of Dermatology (AAD), several research studies on the use of biologics in psoriasis were presented, highlighting the efficacy and safety of these agents in patients with the inflammatory skin disease.
Tildrakizumab Deemed Safe and Effective in Plaque Psoriasis
Treatment with tildrakizumab was associated with high efficacy rates and the anti-interleukin (IL)-23 p19 monoclonal antibody featured a favorable safety profile among patients with moderate to severe plaque psoriasis, according to the results of a study presented at the meeting.1
The study consisted of pooled analyses of the phase 3 reSURFACE 1 (ClinicalTrials.gov Identifier: NCT01722331) and reSURFACE 2 (ClinicalTrials.gov Identifier: NCT01729754) trials. In these studies, patients with moderate to severe plaque psoriasis received treatment with tildrakizumab 100 mg at weeks 0 and 4 and then every 12 weeks thereafter. Clinical improvement in disease activity was evaluated by the proportions of patients who achieved ≥75%, ≥90%, and ≥100% Psoriasis Area and Severity Index (PASI) improvement (PASI 75, 90, and 100 response), as well as Physician’s Global Assessment (PGA) score of 0 or 1 with an at least 2 grade reduction (PGA 0/1) from baseline.
Across all age quartiles (18-36 years, 36-45 years, 45-55 years, and 55-82 years), the proportions of patients who achieved PASI 75, PASI 90, and PASI 100 responses increased over time and peaked at week 28. More than half of patients achieved PASI 75 response by week 12, with continued improvements observed through week 28. A greater proportion of patients aged 18 to 35 years achieved PASI 100 response by week 28 (29.5%). Additionally, the investigators observed similar percentages of patients across all age quartiles who achieved PGA 0/1 with an at least 2 grade decrease from baseline by week 28.
“Median PASI scores trended down quickly for all groups, eventually settling on very low numerical values, which underscores the high level of clearance that the vast majority of patients will experience,” explained study researcher George Han MD, PhD, of the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York.
With respect to safety, the most frequently reported treatment-emergent adverse events (TEAEs) included arthralgia, diarrhea, headache, and nasopharyngitis. Severe TEAEs were observed in up to 5% of patients, but the investigators reported a higher frequency of these severe events in patients aged 45 years and older.
“I think tildrakizumab has always stood out due to its safety,” said Dr Han. “It’s reassuring to see that this is a consistent finding regardless of how the data is cut.”
Dr Han added that a strength of the IL-23 inhibitor class includes the lack of significant contraindications. “It’s an easy decision to start one of these medications, and, within the class, tildrakizumab is notable for its safety and reliability,” he explained.
In terms of future research, Dr Han noted that he would like to see more long-term data across age, weight, and prior treatment groups to further “fill out the story” of the efficacy of tildrakizumab. “I am enthused by numerous real-world studies that have shown higher efficacy rates of tildrakizumab in clinical trials, which is very impressive indeed as we often see the opposite effect,” he added.
Anti-IL-17A Improves Psoriasis in Real-Life Practice
Patients with moderate to severe psoriasis experience benefit with anti-IL-17A biologics, regardless of whether they have previously undergone treatment with a biologic with a different mechanism of action, according to a real-world study presented by Saakshi Khattri, MD, director of the Center for Connective Tissue Diseases at the Icahn School of Medicine at Mount Sinai in New York, New York.2 “Overall, [the findings] reconfirmed what we know via clinical trials and via what we see in our practices,” said Dr Khattri. “When we use all biologics, they work to clear or improve psoriasis.”
The Psoriasis Study of Health Outcomes (PSoHO) included adult patients with psoriasis who either initiated their first biologic therapy (n=1127) or switched biologics (n=645) for the treatment of the disease. Among biologic-naive patients, a greater proportion achieved PASI ≥90 and/or static PGA 0/1 with anti-IL-17A biologics (77%) vs biologics with other mechanisms of action (61%). Among biologic-experienced patients, a greater proportion also achieved PASI ≥90 and/or static PGA 0/1 with an anti-IL-17A agent (65%) vs biologic agents with different mechanisms of action (56%). No comparative analyses were performed, however, and the researchers did not adjust for measured confounders.
Dr Khattri noted that the real-world findings are particularly impactful for practicing clinicians, as they provide “another piece of information” regarding optimal biologic selection for individual patients with psoriasis. “Real-world [data] are always important, as that is close to what we as prescribers see in our offices,” she said, adding that to have data on how agents with specific mechanisms of action fare over others “is helpful in making an informed decision.”
Deucravacitinib Shows Promising Efficacy in Plaque Psoriasis
A study presented at AAD 2023 reported long-term findings from the phase 3 POETYK PSO Program, which included patients with moderate to severe plaque psoriasis who underwent treatment with the oral allosteric tyrosine kinase (TYK) 2 inhibitor deucravacitinib.3 The study findings were presented by Richard Warren, MD, professor of Dermatology and Therapeutics and Honorary Consultant Dermatologist at the University of Manchester in the United Kingdom.
The study analyzed long-term clinical outcomes in patients with approximately 2 years of continuous exposure to the TYK2 inhibitor. In total, 265 patients with moderate to severe plaque psoriasis received continuous treatment with deucravacitinib from day 1 in the POETYK-PSO-1 trial (ClinicalTrials.gov Identifier: NCT03624127) to week 112 in the POETYK PSO-LTE long-term extension study (ClinicalTrials.gov Identifier: NCT04036435).
The study subdivided the cohort into biologic-naive patients (n=157), anti-tumor necrosis factor (anti-TNF)-experienced patients (n=36), and anti-IL-17/anti-IL-23-experienced patients (n=72). At week 12, high clinical responses to deucravacitinib were observed across all patient subgroups, according to PASI and static PGA scores.
Biologics for Prevention of Psoriatic Arthritis
Another study looked at the effects of biologics on preventing the development of psoriatic arthritis in patients with psoriasis.4 The retrospective cohort study compared the incidence of psoriatic arthritis among patients with psoriasis who switched from phototherapy to biologics (n=623) vs those who continued phototherapy (n=1182).
The capped follow-up period was 10 years. Overall, the incidence rate per 1000 person-years for psoriatic arthritis was 49.19. The incidence rates for psoriatic arthritis in the phototherapy and biologic cohorts were 56.83 and 38.77, respectively, a difference that was statistically significant in a multivariable-adjusted analysis (adjusted hazard ratio, 0.69; 95% CI, 0.55-0.88; P =.003).
When asked to comment on the findings, David M. Pariser, MD, of Pariser Dermatology in Norfolk, Virginia, said that it has been widely known that psoriasis is often accompanied with a number of comorbidities, including psoriatic arthritis.
“Psoriatic arthritis is a crippling condition if not treated,” said Dr Pariser, who was not involved in the study. “Dermatologists who see patients with psoriasis earlier on in their course can be a significant help if they’re able to identify early signs of psoriatic arthritis and put people on biologics, which do tend not only to help prevent worsening of disease, but in some cases with some of the biologics has been shown to actually reverse some of the damage to the joints.”
Further Clinical Perspectives
According to Dr Pariser, the development of biologics revolutionized the entire treatment landscape for psoriasis by allowing for better clearance of the disease in many patients. “And for most people, these agents are much safer than the traditional treatments that were used before biologics became available,” he added.
Over the past few years, biologic agents have improved in terms of their efficacy and safety, Dr Pariser commented. “All of the psoriasis clinical trials measure quality of life using some standardized validated measure, and a significant improvement in quality of life occurs.”
Dr Pariser added that given their demonstrated efficacy and safety, biologics have now become standard of care in the treatment of psoriasis. “I’ve been around long enough to remember what it was like before biologics, and it certainly is a much better world now because of it,” he concluded.
Disclosure: The POETYK trials were supported by Bristol Myers Squibb, the PSoHO trial was supported by Eli Lilly and Company, and the reSURFACE 1 and reSURFACE 2 trials were supported by Merck. The authors reported financial affiliations with the pharmaceutical industry.
- Elewski B, Han G, Rozzo SJ, et al. Insights into the efficacy and safety of tildrakizumab in patients with moderate-to-severe plaque psoriasis across age quartiles: pooled analyses from the Phase 3 reSURFACE 1 and reSURFACE 2 trials. Poster presentation at: AAD 2023; March 17-21, 2023; New Orleans, LA. Poster 42297.
- Khattri S, Gooderham M, Reich A, et al. The Psoriasis Study of Health Outcomes (PSoHO) in biologic-naïve and -experienced patients: a post-hoc analysis of patients receiving treatment according to US labels. Poster presentation at: AAD 2023; March 17-21, 2023; New Orleans, LA. Poster 43054.
- Warren RB, Armstrong AW, Imafuku S, et al. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: 2-year efficacy by prior biologic treatment in the phase 3 POETYK PSO program. Poster presentation at: AAD 2023; March 17-21, 2023; New Orleans, LA. Poster 43879.
- Miao K, Huang M, Xepoleas M, et al. Do biologics for psoriasis prevent the development of psoriatic arthritis? A population-based study. Poster presentation at: AAD 2023; March 17-21, 2023; New Orleans, LA. Poster 42744.