The safety and frequency of adverse events with spesolimab treatment

Introduction

Dysregulation of the IL-36 pathway has been implicated in several inflammatory diseases, such as generalized pustular psoriasis (GPP), palmoplantar pustulosis, and atopic dermatitis. Spesolimab, a first-in-class anti-interleukin (IL)-36R antibody, has been shown to be efficacious and safe for the management of GGP flares.

Spesolimab was recently granted Food and Drug Administration (FDA) approval for the treatment of GPP flares, as previously reported on the Psoriasis and Psoriatic Arthritis Hub. At the 2022 European Academy of Dermatology and Venereology Congress (EADV), Mockenhaupt presented safety data from five clinical trials investigating spesolimab.¹

Study design¹ 

The five clinical trials include a phase I trial (NCT02978690) and four phase II, double-blind, randomized placebo-controlled trials (NCT03782792; NCT03135548; NCT04015518; NCT03822832). A detailed summary of the studies is shown in Table 1. Across the five studies, 222 patients were treated with spesolimab and 100 patients received placebo.

Table 1. Study details*

Safety¹

The rate ratio of adverse events (AEs) for spesolimab versus placebo was 1.3, 0.9, 0.9, and 1.2 for studies 2, 3, 4, and 5, respectively. Adverse event occurrence, including severe and serious AEs, is shown in Figure 1; there were no patient deaths reported across the five studies. Infections were mostly mild and uncomplicated, the most common are outlined in Figure 2. Two of the placebo-controlled trials demonstrated a lower infection rate in the spesolimab group (Trial 3 and Trial 4), while two showed a lower infection rate in the placebo group (Trial 2 and Trial 5). Upper respiratory tract infections were most common but others, such as urinary tract infections, were also reported.

Figure 1. Incidence of adverse events* 

AE, adverse event.
*Adapted from Mockenhaupt.^1
†Rheumatology Common Toxicity Criteria ≥3.
^‡A patient may have serious adverse events with multiple seriousness criteria.

Figure 2. Overall infection rate and most common infection per study* 

*Adapted from Mockenhaupt.¹

Rates of hypersensitivity (eczema, rash, allergic rhinitis, and drug reaction with eosinophilia and systemic symptoms), anaphylactic reactions (including circulatory collapse), and angioedema (eye oedema and urticoria) were evaluated in Studies 2, 4, and 5. There was a similar frequency of hypersensitivity between the placebo and spesolimab groups, with the highest frequency observed in Study 5 (33.3% and 44.4% in the spesolimab and placebo arms, respectively). Eosinophil values were also measured for all five trials, there was no evidence of eosinophilia associated with spesolimab treatment. High eosinophils (>1 × 10⁹/L) were observed in two patients (28.6%) in Study 1 and four patients in the placebo (28.6%) and four patients in the spesolimab (12.9%) arm of Study 5. For all other trials, no patients in either arm were found to have a high eosinophil count. Although elevation in liver enzymes was recorded, this was not found to be associated with spesolimab treatment.

Conclusion¹ 

Analysis of these five clinical trials showed a similar frequency of AEs between the placebo and treatment arms. Spesolimab was shown to have a favorable safety profile, with no evidence of treatment-associated eosinophilia in patients with GPP, palmoplantar pustulosis, or atopic dermatitis; however, this was in a limited number of patients. This data and its recent FDA approval suggest spesolimab could prove an effective treatment option for patients with GPP and other chronic inflammatory diseases.