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What factors cause multiple biologic failure in psoriasis?



Female sex, hyperlipidemia, Medicaid insurance, earlier year of biologic initiation, shorter duration of psoriasis, and prior nonbiologic systemic therapy use were associated with multiple biologic failure in patients with psoriasis, results from a prospective cohort demonstrated.

“Prior cross-sectional and single-center studies have primarily analyzed therapeutic failure of a single biologic or biologics within one class,” researchers led by Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, wrote in the study, published in the Journal of the American Academy of Dermatology. “However, failure of multiple biologics targeting different signaling pathways is common over the course of treatment. These ‘multiple biologic failure’ patients are not well-characterized, and the patterns of biologics attempted and sociodemographic or clinical features that may predict difficult treatment are incompletely studied.”

To bridge this gap, the researchers conducted a prospective cohort study from the CorEvitas Psoriasis Registry, which collected data from dermatologist-diagnosed patients with psoriasis who started or switched to a Food and Drug Administration (FDA)–approved systemic therapy for psoriasis during routine dermatology visits from April 15, 2015, to May 10, 2022. This period included data from 17,196 patients across 259 private and 209 academic sites from 580 physicians in the United States and Canada.

From this registry, Dr. Liao and colleagues identified 1,039 patients with 24 months or more of follow-up data, a confirmed index biologic start date, and valid baseline assessment data, and categorized them into three cohorts:

  • 490 (47.2%) with good response (GR), defined as patients with 24 months or more of continued index biologic use by the last registry visit.
  • 65 (6.3%) with multiple biologic failure (MBF), defined as patients administered two or more biologic agents of different mechanistic classes who discontinued these biologics because of physician-reported “inadequate initial response,” “failure to maintain initial response,” or “active disease” despite 90 or more days of use per biologic.
  • 484 (46.6%) categorized as “other,” defined as patients failed by one biologic or who discontinued treatment for nonmedical reasons.

The researchers used multivariable logistic regression to identify sociodemographic, clinical, and patient-reported outcomes that differed between the MBF and GR groups. The mean age of the patients in the study was 49.1 years, 44.2% were female, 77.9% were White, 9.7% were Hispanic, and the mean duration of psoriasis was 11.5 years.

On multivariable logistic regression, factors associated with MBF, compared with those with GR, included female at birth (odds ratio [OR] = 2.29; confidence interval [CI], 1.11-4.72), history of hyperlipidemia (OR = 3.14; CI, 1.35-7.30), Medicaid insurance (OR = 4.53; CI, 1.40-14.60), prior nonbiologic systemic therapy (OR = 2.47; CI, 1.16-5.25), higher psoriasis duration (OR = 0.60 per standard deviation [SD]; CI, 0.38-0.94), and later index biologic initiation (OR = 0.37 per year; CI, 0.27-0.52). Sensitivity analysis revealed that the duration of prior nonbiologic systemic therapy use was not associated with MBF (OR = 0.99; CI, 0.94-1.02; P = 0.56).

“Interestingly, health-related behaviors (e.g., smoking, alcohol use) and location/extent of psoriasis were not important differentiators between MBF and GR,” the authors noted. “We might suspect these features to correlate with MBF, as numerous observational studies found associations between health-related behaviors or psoriasis severity and presence at difficult-to-treat locations, which often relates to biologic use.”

They acknowledged certain limitations of their study, including underrepresentation of ethnoracial minorities and male sex at birth relative to reported psoriasis epidemiology, “possibly reflecting participation bias and reduced access to specialty care, given that patients were enrolled into the registry by dermatologists,” they wrote. “Patient adherence to prescribed biologic regimens between registry visits was not evaluated.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that despite the rapid expansion in biologic therapies for psoriasis, “analysis of real-world use patterns and patient characteristics has been limited – particularly for those who have failed multiple treatments. These findings suggest that there indeed may be some key differences between patients who have had to cycle through multiple biologics versus those who have had a sustained satisfactory response on a single therapy, such as disease duration and previous nonbiologic treatments.”

Dr. Raj Chovatiya, department of dermatology, Northwestern University, Chicago Dr. Chovatiya

Dr. Raj Chovatiya

However, he added, “while this prospective study utilized a robust approach to gather standard-of-care data across multiple clinical sites, the absolute number of patients with multiple biologic failures was low, and additional data for these kinds of patients are still highly needed.”

The study was sponsored by CorEvitas and supported through a partnership between CorEvitas and the National Psoriasis Foundation. Dr. Liao disclosed that he has received research grant funding from AbbVie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. Dr. Chovatiya disclosed ties with several pharmaceutical companies.

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