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PARIS -- Off-label use of biologic agents to treat refractory atopic dermatitis posed a significant risk of serious infection as compared with systemic nonbiologic agents, data on almost 400,000 patients showed.

A propensity-matched analysis showed that treatment with a biologic agent doubled the risk of hospitalization for a serious bacterial or opportunistic infection as compared with high-potency topical steroids or nonbiologic systemic therapy. Infection risk also varied substantially among nonbiologic systemic agents, with cyclosporine posing the lowest risk and azathioprine and mycophenolate the greatest risk, as reported here at the congress.

"This is the largest comparative safety evaluation of its kind to date in adult patients with atopic dermatitis," said Mia Schneeweiss, a student at Harvard Medical School and Brigham and Women's Hospital in Boston. "Biologics were associated with a greater risk of serious infection requiring hospitalization than either nonbiologic systemics or topical steroids."

The analysis did not include patients treated with newer biologic agents specifically approved for atopic dermatitis, such as dupilumab (Dupixent). Investigators intend to update the analysis with data on outcomes with the newer agents, as well as long-term outcomes with all the treatments, she added.

The study had its genesis in the increasing use of systemic nonbiologic immunomodulatory drugs and systemic biologic agents to treat atopic dermatitis that is inadequately controlled by topical steroids. Mixed results have emerged from studies use of biologic agents to treatment recalcitrant atopy; however, experience with systemic biologic and nonbiologic agents in other conditions (such as psoriasis and rheumatoid arthritis) has shown an increased risk of bacterial infections, Schneeweiss noted.

"Few population-based studies have evaluated the safety of off-label use of these systemic agents for treating severe atopic dermatitis," she said. "Additionally, comparative safety data among nonbiologic and biologic immunomodulatory agents in the treatment of atopic dermatitis is limited."

In an effort increase the evidence base, investigators undertook an analysis of a commercial insurance claims database encompassing 2003-2016 and 180 million lives. They used diagnostic codes to identify all adults with a diagnosis of atopic dermatitis and initiating treatment. Patients with other indications for any of the medications of interest (psoriasis, arthritis, organ transplantation, etc.) were excluded.

The primary outcome was first occurrence of hospitalization for a serious bacterial or opportunistic infection. Patient characteristics were assessed 6 months before the study and followed for an additional 6 months.

The study consisted of two cohort analyses. The first involved patients who initiated treatment with a low-potency topical corticosteroid and subsequently had treatment escalation to one of three therapeutic categories: high-potency topical corticosteroids, biologics and disease-modifying drugs (including anti-TNF agents, rituximab [Rituxan], and tofacitinib [Xeljanz], and nonbiologic systemic therapy (methotrexate, cyclosporine, azathioprine, prednisone, and mycophenolate).

The second cohort comprised patients who started treatment with any type of topical corticosteroid and subsequently had treatment escalation to a biologic or systemic nonbiologic agent.

The first cohort included 396,734 patients who initiated treatment with a high-potency topical corticosteroid and 403 patients who started treatment with a biologic agent. The second cohort included 153,890 patients who initiated treatment with a systemic nonbiologic agent and 2,116 who who started a biologic drug.

In the first cohort, patients who escalated to a high-potency topical steroid had a total of 1,039 qualifying hospitalizations for serious infection, resulting in a rate of 2.62 per 1,000. That compared with 16 events in the 403 patients who initiated treatment with a biologic agent, resulting in a rate of 39.70 per 1,000. An unadjusted analysis produced a relative risk of 15.16 for patients treated with biologics.

The second cohort analysis showed 1,239 hospitalizations for infection in the patients who were new users of systemic nonbiologic agents (8.05/1,000) versus 47 hospitalizations among new users of biologic therapies (22.21/1,000). Comparison of the two groups yielded a relative risk of 2.76 for the patients who received biologic therapy.

A multivariate analysis with propensity matching yielded similar relative risks for the two cohorts: 2.74 for the comparison of biologics versus high-potency topical corticosteroids and 2.16 for the comparison of biologics versus systemic nonbiologic agents.

Investigators also compared the relative risk of infection-related hospitalization for the five systemic nonbiologic agents. Cyclosporine emerged with the lowest overall relative risk, ranging from 0.17 to 0.55 in comparisons with other four systemic nonbiologic, followed by prednisone and methotrexate. Mycophenolate was associated with the highest relative risk (1.64 to 5.88), and azathioprine had a two- to fourfold higher risk versus all other agents except mycophenolate (0.61).

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