How is GPP distinct from PsO?

GPP has a distinct pathogenic mechanism and treatment response from plaque psoriasis (PsO)^1-4

Rare and potentially life-threatening
Rapid onset (for GPP flares)
Systemic symptoms are common
Relapsing and persistent skin disease
Innate immune inflammation
Primarily driven by the IL-36 pathway
Significantly higher mortality risk vs plaque psoriasis^a

Common
Gradual onset
Persistent skin disease
Adaptive immune response
Primarily driven by the IL-23/IL-17 pathway

GPP is driven by dysregulated IL-36R signaling, while
PsO is primarily driven by the IL-23/IL-17 pathway^2-4,7

^aAn observational study using US claim data between January 1, 2015 and December 31, 2020 that included 1,246 patients with GPP (ICD 10 code L40.1), 2,630 All-GPP (GPP only and GPP with plaque psoriasis) patients and 127,540 plaque psoriasis (L40.0) patients. At the maximum follow-up (adjusted), the GPP-only and All-GPP cohorts exhibited over 1.5 times higher risk of mortality than the plaque psoriasis-only cohort (hazard ratio 1.55, 95% confidence interval 1.14–2.11, P=0.005; hazard ratio 1.61, 95% confidence interval 1.30–1.99, P<0.001, respectively).⁷

FAQ

Why is it important to target the IL-36 pathway in GPP?

Learn more by watching this video

Watch expert, Dr. Adam Friedman, Professor and Chair of Dermatology at George Washington University School of Medicine and Health Sciences, explain the role of the IL-36 pathway in GPP and how SPEVIGO could help treat your patients with GPP.

Please see Important Safety Information below.

Dr. Adam Friedman has been compensated for his time.

Transcript

The IL-36 signaling pathway is the primary driver in the pathogenesis of generalized pustular psoriasis, or GPP. Pro-inflammatory IL-36 signaling triggers an innate inflammatory response. SPEVIGO specifically inhibits IL-36 signaling. By binding to the IL-36 receptor SPEVIGO prevents downstream activation of pro-inflammatory pathways.

For my GPP patients, my goals are simple: to treat any acute flares, reduce the risk of future flares, and of course, manage chronic symptoms of the disease. SPEVIGO is the only FDA-approved treatment that addresses the acute and chronic symptoms of GPP.

GPP, generalized pustular psoriasis; ICD, International Classification of Diseases; IL, interleukin; IL-36R, interleukin-36 receptor; PsO, plaque psoriasis.

Learn how SPEVIGO is designed to treat GPP

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Indication

SPEVIGO is indicated for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients 12 years of age and older and weighing at least 40 kg (88 lb).

Please see SPEVIGO Prescribing Information, including Medication Guide.

Important Safety Information

Contraindications

SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO. Reported hypersensitivity reactions have included drug reaction with eosinophilia and systemic symptoms (DRESS) and anaphylaxis.

WARNINGS AND PRECAUTIONS

Infections: SPEVIGO may increase the risk of infections. In patients with a chronic infection or a history of recurrent infection, consider the potential risks and expected clinical benefits of treatment prior to prescribing SPEVIGO. Treatment with SPEVIGO is not recommended in patients with any clinically important active infection until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur during or after treatment with SPEVIGO. If a patient develops a clinically important active infection, discontinue SPEVIGO therapy until the infection resolves or is adequately treated.

Risk of Tuberculosis: 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.

Hypersensitivity and Infusion-Related Reactions:

Serious hypersensitivity reactions, including anaphylaxis and delayed reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during and following administration of SPEVIGO. These reactions can occur with the first dose or subsequent doses.
SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO. If a patient develops signs of anaphylaxis or other serious hypersensitivity, discontinue SPEVIGO immediately and initiate appropriate treatment.
If a patient develops mild or moderate hypersensitivity during an intravenous infusion or other infusion-related reactions, stop SPEVIGO infusion and consider appropriate medical therapy (eg, systemic antihistamines and/or corticosteroids). Upon resolution of the reaction, the infusion may be restarted at a slower infusion rate with gradual increase to complete the infusion.

Vaccinations: Prior to initiating SPEVIGO for treatment of GPP, complete all age-appropriate vaccinations according to current immunization guidelines. Avoid use of live vaccines in patients during and for at least 16 weeks after treatment with SPEVIGO. No specific studies have been conducted in SPEVIGO-treated patients who have recently received live viral or live bacterial vaccines.

ADVERSE REACTIONS

Intravenous SPEVIGO for Treatment of GPP Flare (Study Effisayil-1): Most common adverse reactions reported in ≥5% of patients treated with SPEVIGO in the clinical trial were asthenia and fatigue, headache, nausea, pruritus and prurigo, infusion site hematoma and bruising, and urinary tract infection (UTI).

Specific Adverse Reactions

Infections: The most frequent adverse reactions that occurred in subjects treated with intravenous SPEVIGO were infections. During the 1-week placebo-controlled period in Study Effisayil-1, infections were reported in 14% of subjects treated with SPEVIGO compared with 6% of subjects treated with placebo. Serious infection (UTI) was reported in 1 subject (3%) in the SPEVIGO group and no subjects in the placebo group. Infections observed through Week 1 in Study Effisayil-1 in subjects treated with SPEVIGO were mild (29%) to moderate (71%).
Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Two cases of DRESS were reported in Study Effisayil-1 in subjects with GPP who were treated with intravenous SPEVIGO. RegiSCAR DRESS validation scoring (with the following categories: “no,” “possible,” “probable,” or “definite” DRESS) was applied to the reported cases. Reported cases were assessed as “no DRESS” and “possible DRESS.”

Subcutaneous SPEVIGO for Treatment of GPP When Not Experiencing a Flare (Study Effisayil-2): Regarding the exposure-adjusted incidence rates for subjects on randomized treatment prior to receiving rescue treatment for flare or completing trial without a flare, the rate per 100-patient years for injection site reaction (including erythema, pain, swelling, induration, urticaria, and warmth at the injection site) was 31.6 for the subcutaneous SPEVIGO cohort (600 mg loading dose followed by 300 mg every 4 weeks) vs 12.7 for the placebo cohort. The rate per 100-patient years for UTI was 18 for SPEVIGO vs 0 for placebo. The rate per 100-patient years for pruritus was 8.8 for SPEVIGO vs 0 for placebo. The rate per 100-patient years for arthralgia was 13.3 for SPEVIGO vs 6 for the placebo cohort. There were 3 subjects who discontinued subcutaneous SPEVIGO due to treatment-emergent adverse events of psoriasis compared to no subjects in the placebo cohort who discontinued placebo for any treatment-emergent adverse event.

Safety in Study Effisayil-2 After Flare: In Effisayil-2, subjects who experienced a GPP flare and received at least one dose of an open-label single intravenous 900 mg dose of SPEVIGO were treated with open-label subcutaneous SPEVIGO 300 mg. These subjects (n=19) received subcutaneous dosing at every 12 weeks, which could have been increased to every 4 weeks based on GPPPGA total score or pustulation subscore increased by ≥1 from any previous open-label maintenance visit. The reported safety profile of open-label subcutaneous SPEVIGO use after treatment of GPP flare with open-label intravenous SPEVIGO use was consistent with the safety profiles of use of SPEVIGO from Trial Effisayil-1 and randomized controlled data from Trial Effisayil-2.

Clinical Development of Spesolimab-sbzo

Guillain-Barre Syndrome (GBS): Among approximately 835 subjects exposed to spesolimab-sbzo during clinical development, GBS was reported in 3 subjects who received various doses of spesolimab-sbzo via various methods of administration in clinical trials for unapproved indications.

SPECIFIC POPULATIONS

Pediatric Use: The safety and effectiveness of SPEVIGO for the treatment of GPP have been established in pediatric patients 12 years of age and older and weighing at least 40 kg. Use of SPEVIGO for this indication is supported by data from a randomized, placebo-controlled study, which included 6 pediatric subjects 14 to 17 years of age with a history of GPP treated with subcutaneous SPEVIGO (Study Effisayil-2), and evidence from an adequate and well-controlled study of intravenous SPEVIGO in adults with GPP (Study Effisayil-1), with additional pharmacokinetic analyses showing similar drug exposure levels in adults and pediatric subjects 12 years of age and older and weighing 40 kg or more. 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.

Please see SPEVIGO Prescribing Information, including Medication Guide.

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References

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Johnston A, Xing X, Wolterink L, et al. IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J Allergy Clin Immunol. 2017;140(1):109-120. doi:10.1016/j.jaci.2016.08.056
Furue K, Yamamura K, Tsuji G, et al. Highlighting interleukin-36 signalling in plaque psoriasis and pustular psoriasis. Acta Derm Venereol. 2018;98(1):5-13. doi:10.2340/00015555-2808
Schön MP, Erpenbeck L. The interleukin-23/interleukin-17 axis links adaptive and innate immunity in psoriasis. Front Immunol. 2018;9:1323. doi:10.3389/fimmu.2018.01323
Strober B, Kotowsky N, Medeiros R, et al. Unmet medical needs in the treatment and management of generalized pustular psoriasis flares: evidence from a survey of Corrona Registry dermatologists. Dermatol Ther (Heidelb). 2021;11(2):529-541. doi:10.1007/s13555-021-00493-0
Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Rev Clin Immunol. 2019;15(9):907–919. doi:10.1080/1744666X.2019.1648209
Gottlieb AB, Kwiatkowski HC, Semeco J, Lakshminarasimhan B, Strober B, Lebwohl M. All-cause mortality is higher in generalized pustular psoriasis (GPP) than plaque psoriasis and the general population: a US-based claims analysis. J Psoriasis Psoriatic Arthritis. Published online May 30, 2025. doi:10.1177/24755303251344155
Burden AD, Kirby B. Psoriasis and related disorders. In: Griffiths CEM, Barker J, Bleiker T, Chalmers R, Creamer D, eds. Rook’s Textbook of Dermatology. 9th ed. John Wiley & Sons; 2016:chap 35.