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A systematic review has found relatively low short- and long-term risk of infection and malignancy in patients with psoriasis receiving IL-17 inhibitors and IL- 23 inhibitors.

The review, which appeared in , included 45 randomized controlled trials and 27 open-label extension studies. For people taking IL-17 inhibitors, respective short-term risks of serious infection, overall infection, and malignancy were 1.45 (95% CI 0.81-2.59), 1.20 (95% CI 1.06-1.35), and 0.83 (95% CI 0.41-1.71). This patient group did, however, see in increased short-term risk of nasopharyngitis and Candida infection.

For those taking IL-23 inhibitors, risks were 0.68 (95% CI 0.38-1.22) for serious infection, 1.13 (95% CI 1.00-1.28) for overall infection, and 0.87 (95% CI 0.37-2.04) for malignancy.

The study was led by a team of researchers based in Chengdu, China. The following study excerpts have been edited for length and clarity.

What was the context for developing this review?

In addition to being implicated in the pathogenesis of psoriasis, the IL-17 family and IL-23 perform fundamental functions in innate and adaptive immunity. Hence, concerns about infection and malignancy associated with deficiency of IL-17 or IL-23 immunity have been raised, especially in patients receiving long-term therapies.

To date, IL-17 inhibitors and IL-23 inhibitors have been proven generally safe and well-tolerated. However, individual trials lack large sample sizes or long-term trial durations to detect the risk of rare adverse events such as serious infections and malignancies.

Comprehensive studies that generalize and quantify current safety data, particularly long-term data, are lacking. The researchers aimed to fill that gap by evaluating the short- and long-term safety profiles of IL-17 or IL-23 inhibitors, assessing risk for the short-term risk and long-term incidence rates of overall infection, serious infection, malignancy, nasopharyngitis, upper respiratory tract infection, Candida infection, tuberculosis, hepatitis, and herpes zoster.

What were the key findings?

The results suggested that anti-IL-17 and anti-IL-23 treatments did not increase the short-term risk of serious infection or malignancy in adults with psoriatic disease. Correspondingly, the long-term incidence rates of serious infection and malignancy were quite low, in particular the incidence rate of malignancy (less than 1/100 person-years).

Despite the enhanced short-term risks of overall infection and some specific infections with both IL-17 inhibitors and IL-23 inhibitors, the risk ratios were moderately increased. The long-term incidence rates of overall infection were estimated to be 57.78/100 person years with IL-17 inhibitors and 48.5/100 person-years with IL- 23 inhibitors.

What did the review find regarding Candida infection?

Candida infection appeared to be a prominent adverse event for IL-17 inhibitors. This study suggested that the short-term risk of Candida infection was approximately 3-fold higher with IL-17 antagonists compared with placebo. The long-term incidence rate was estimated to be 3.41/100 person years.

In addition, the risk of Candida infection was increased almost 6-fold when bimekizumab was used, which appeared to be higher than other IL-17 inhibitors.

What is the key takeaway message for dermatologists?

Continued vigilance for Candida infection will be required during treatment with IL-17 inhibitors.

IL-17 inhibitors and IL-23 inhibitors are both generally safe in the treatment of psoriasis and psoriatic arthritis. Nasopharyngitis and upper respiratory tract infection are the most frequent adverse events, and Candida infection seemed to be the most common opportunistic infection. Caution and ongoing vigilance for nasopharyngitis and Candida infection, particularly in patients receiving IL-17 inhibitors, are crucial.

Key points

• IL-17 and IL-23 inhibitors are both generally safe for treating psoriatic disease, with low short- and long-term risk for infection and malignancy.
• Candida infection, upper respiratory tract infection, and nasopharyngitis were the most common adverse events.
• Candida risk was particularly high for IL-17 inhibitors; clinical vigilance advised.