麻豆传媒

The risk of serious infection varied among biologic and targeted agents used to treat moderate-to-severe psoriasis but overall was low across the drug classes, a large retrospective review showed.

As compared with an etanercept (Enbrel) reference rate, adalimumab (Humira) and infliximab (Remicade) led to higher rates of serious infection among new users. Patients starting ustekinumab (Stelara) had a lower rate versus the references. The infection rate versus etanercept was similar for new users of other biologics, biosimilars, and targeted agents.

Concomitant use of nonsteroidal anti-inflammatory drugs or systemic steroids increased the risk of serious infection for all of the drugs evaluated, reported Emilie Sbidian, MD, PhD, of Henri Mondor Hospital in Crèteil, France, and colleagues, in .

"The most frequent serious infections were gastrointestinal, skin, and subcutaneous tissue and pulmonary infections," the authors wrote. "This distribution of the serious infections was expected, but with an unexpectedly high proportion of gastrointestinal serious infections in our study (especially cholangitis and diverticulitis). These variations could be attributable to the differences between national healthcare systems, leading to differences in hospitalization rates for serious infection."

Relatively few patients had prescriptions for some of the newer drugs. Other observational studies are needed to confirm the results, the team added.

Reassuring Data

A key takeaway from the analysis is the low overall rate of serious infection, according to Joel Gelfand, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia and an expert spokesperson for the American Academy of Dermatology.

"The study is largely reassuring," he told 麻豆传媒 in an email. "First, the overall rate of serious infections is quite low in this population of psoriasis patients in France treated with biologics or apremilast [Otezla]. Second, in general, the rate of infection was similar in the various treatments compared to etanercept. The main exception is infliximab, which had a slightly higher risk, and ustekinumab, which had a slightly lower risk. Adalimumab, had a slightly higher risk compared to etanercept in the primary analysis, but this finding did not hold up with additional analyses."

Gelfand also noted some limitations of the study: "First, rheumatoid arthritis is a common indication for TNF [tumor necrosis factor] inhibitors, so ideally the authors should have excluded these patients from the analysis. Second, in the U.S., etanercept is now uncommonly used for psoriasis as its efficacy is not as good as other available biologic options. Therefore, a more clinically relevant comparator would have been a more commonly used biologic for psoriasis. Third, it is not clear if the rates observed are any different than expected in people with psoriasis as no comparator was studied."

"Due to the small absolute differences in risk, when differences were identified, and the limitations of the study design, the clinical significance of these findings is uncertain," Gelfand added. "Clinicians need to weigh treatment benefit, the patient's underlying comorbidities, and preferences when deciding on an optimal treatment for psoriasis."

The therapeutic landscape for psoriasis has changed dramatically in recent years and continues to evolve. The rapid emergence of new agents has created a need for comparative safety studies in real-world settings, Sbidian and co-authors noted. Clinical trials supporting regulatory approval lacked adequate statistical power to assess the risk of serious infection, and prior observation studies yielded conflicting results and used different analytic methods, making them difficult to compare.

Sbidian and colleagues conducted a retrospective observational study designed to address some of the limitations of prior studies. Data for the analysis came from the French national health data system, which covers 99% of France's population.

Study Design, Results

The investigators identified all adults with psoriasis, which was defined as patients who received at least two prescriptions for a topical vitamin D derivative within a 2-year period and registered in the database from Jan. 1, 2008 to May 31, 2019. From that population, the team identified patients who were new users of biologic agents or apremilast.

The analysis included 44,239 patients who had a median age of 48.4 and a median follow-up of 12 months. TNF inhibitors accounted for 29,618 (66.9%) new users, interleukin (IL)-12/23 inhibitors for 6,658 (15%), IL-17 inhibitors for 4,093 (9.3%), anti-IL-23 for 526 (1.2%), and apremilast for 3,344 (7.6%).

The primary outcome was the incidence of serious infection, defined as a hospital discharge diagnosis with an ICD-10 diagnostic code associated with infection.

The patient records revealed 1,656 serious infections, resulting in a crude overall incidence of 25.0 per 1,000 person-years. Gastrointestinal infections accounted for 645 (38.9%) of the total, followed by skin (324, 19.6%) and pulmonary (245, 14.8%) infections. Median time to an event was 9 months.

Compared with patients treated with etanercept, new users of other biologics, biosimilars, or targeted agents had the following hazard ratios for serious infection:

• Infliximab: HR 1.79 (95% CI 1.49-2.16)

• Guselkumab (Tremfya): HR 1.37 (95% CI 0.70-2.67)

• Adalimumab: HR 1.22 (95% CI 1.07-1.38)

• Certolizumab (Cimzia): HR 1.15 (95% CI 0.83-1.59)

• Ustekinumab: HR 0.79 (95% CI 0.67-0.94)

• Brodalumab (Siliq): HR 0.79 (95% CI 0.21-2.95)

• Ixekizumab (Taltz): HR 0.82 (95% CI 0.50-1.35)

• Apremilast (Otezla): HR 0.83 (95% CI 0.63-1.10)

• Secukinumab (Cosentyx): HR 0.94 (95% CI 0.75-1.18)

Study limitations, the researchers said, included that the definition of psoriasis used was based on topical vitamin D prescriptions; that the definition of drug exposure/adherence was inexact; and that the identification of serious infections was based on discharge diagnosis only.

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