If GPP flare symptoms persist, an additional intravenous 900 mg dose (over 90 minutes) may be administered one week after the initial dose.

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SPEVIGO. Avoid use of SPEVIGO in patients with active TB infection.

Consider initiating anti-TB therapy prior to initiating SPEVIGO in patients with latent TB or a history of TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SPEVIGO treatment.

SPEVIGO-associated hypersensitivity reactions may include immediate reactions such as anaphylaxis and delayed reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety and effectiveness of SPEVIGO in pediatric patients younger than 12 years of age or in pediatric patients weighing less than 40 kg have not been established.

There were 2 (6%) intravenous SPEVIGO-treated subjects 65 to 74 years of age and no subjects 75 years of age or older in Study Effisayil-1. There were 6 (7%) subcutaneous SPEVIGO-treated subjects 65 to 74 years of age and 1 (1%) subject 75 years of age in Study Effisayil-2. Clinical studies of SPEVIGO did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

Spesolimab-sbzo is a humanized monoclonal immunoglobulin G1 antibody that inhibits interleukin-36 (IL-36) signaling by specifically binding to the IL36R. Binding of spesolimab-sbzo to IL36R prevents the subsequent activation of IL36R by its ligands (IL-36 α, β and γ) and downstream activation of pro-inflammatory and pro-fibrotic pathways. The precise mechanism linking reduced IL36R activity and the treatment of flares of GPP is unclear.

The pharmacodynamics of SPEVIGO in the treatment of patients with GPP have not been fully characterized.

When administered intravenously, spesolimab-sbzo AUC increased dose-proportionally from 0.3 to 20 mg/kg, and CL and terminal half-life were independent of dose. Following subcutaneous single dose administration, spesolimab-sbzo exposure increased slightly more than dose-proportionally across the dose range of 150 mg to 600 mg due to increased bioavailability at higher doses.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of spesolimab-sbzo or of other spesolimab products.

In subjects with GPP treated with intravenous SPEVIGO in Study Effisayil-1, ADAs formed with a median onset of 2.3 weeks. Following administration of 900 mg intravenous SPEVIGO, (12/50) 24% of subjects had a maximum ADA titer greater than 4000 and were neutralizing antibody (Nab)-positive by the end of the study (Weeks 12 to 17). In Study Effisayil-2, ADAs formed with a median onset of 8 weeks. Following administration of a 600 mg subcutaneous LD of SPEVIGO followed by 300 mg every 4 weeks for a total duration of 48 weeks, 24% of subjects had a maximum ADA titer greater than 4000 and were Nab-positive.

In Study Effisayil-1 following intravenous SPEVIGO, females appeared to have higher immunogenicity response; the percentage of subjects with ADA titer greater than 4000 was 30% in females, and 12% in males, respectively. In Study Effisayil-2 following administration of subcutaneous SPEVIGO, the data on immunogenicity response in males versus females were inconclusive.

Carcinogenicity and mutagenicity studies have not been conducted with spesolimab-sbzo.

No adverse effects on fertility were observed in male or female mice that were intravenously administered a surrogate antibody to IL36R at doses up to 50 mg/kg twice weekly.