Abstract
Introduction
Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening form of psoriasis, characterized by widespread sterile pustules and systemic symptoms. While the pathogenesis remains incompletely understood, the interleukin 36 (IL-36) pathway has emerged as a key contributor. Spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, has shown rapid and marked clinical improvement in patients during acute GPP flares.
Case Presentation
We report three cases of GPP flares treated with spesolimab in Denmark, administered prior to its commercial availability through a compassionate use program. All patients presented with severe GPP and were assessed using the Physician’s Global Assessment for Generalized Pustular Psoriasis. Treatment with spesolimab resulted in rapid improvement across all cases.
Conclusion
These real-world observations support the clinical efficacy of spesolimab for managing acute GPP flares and demonstrate its potential as a therapeutic option in severe cases, even before commercial access.
Keywords: Case reports, Compassionate use, Pustular psoriasis, Spesolimab
Introduction
Here we report real-world observations of the compassionate use of spesolimab in Denmark for management of generalized pustular psoriasis (GPP). GPP is a rare variant of psoriasis characterized by numerous sterile pustules in the skin. Acute flares of GPP often coincide with systemic symptoms and may lead to life-threatening conditions necessitating hospitalization [1, 2]. The pathogenesis and underlying mechanisms involved in GPP are not fully understood. However, the interleukin 36 (IL-36) pathway seems to play a pivotal role [3]. Spesolimab, the first drug approved for GGP, is a humanized monoclonal antibody targeting the IL-36 receptor and has shown fast and marked improvement in patients with GPP [4, 5]. Utilization of spesolimab in real-world clinical settings has not been reported. By establishing a compassionate use program, we were able to facilitate and evaluate the administration of spesolimab as a therapeutic option for GPP patients, even before it became commercially available. To evaluate the severity of GPP, we applied the Physician’s Global Assessment for Generalized Pustular Psoriasis (GPPGA).
Case Presentations
The first patient enrolled in the compassionate use program was a 35‐years‐old male with a history of psoriasis vulgaris since the age of 24. Prior therapeutic treatments included topical corticosteroids in conjunction with UVB therapy and methotrexate. In January 2021, the patient was discontinued from a clinical trial with roflumilast. In March 2021, the patient was admitted to hospital due to a sudden exacerbation of GPP. Widespread pustules were seen and the patient reported skin tightness, without accompanying fever or systemic symptoms. The day before hospitalization, treatment with clobetasol propionate was initiated. Upon admission, the patient’s GPPGA score was 2. The patient was treated uncomplicated with intravenous infusion of 900 mg spesolimab and discharged immediately after.
At the 7-day follow-up examination, the patient reported improvement in the skin and reduction in skin tenderness. The patient had sporadically used clobetasol propionate since his discharge. No pustules were detected, and scaling had decreased; however, prominent inflammation was still present.
Four weeks following the administration of spesolimab, clobetasol propionate was still applied on a weekly basis. Objectively, there were no pustules, although the inflammation persisted and scales had reappeared, prompting the initiation of adalimumab. Notably, throughout the subsequent year, the patient did not experience recurrence of a pustular flare (Fig. 1, 2) and no side effects to spesolimab were reported.
Fig. 1.
Skin development before (day 0) and after (day 7 and day 28) spesolimab treatment for patient case number 1 and 2 at days 0, 7, and 28.
Fig. 2.
Timeline illustrating the clinical course and progression of disease in each of the 3 patients in relation to different treatments. GPPGA, Physician’s Global Assessment for Generalized Pustular Psoriasis; PASI, Psoriasis Area and Severity Index.
The second patient was a 54-year-old male, diagnosed with psoriasis vulgaris at the age of 11. In 2012, the patient experienced a single episode of psoriasis vulgaris with a pustular flare. Previously, the patient had undergone various therapeutic interventions, including acitretin, UVB therapy, coal tar treatments, and most recently, methotrexate. In the week leading up to the outpatient clinic visit, the patient developed general symptoms and an exacerbation of his psoriasis. Treatment with dicloxacillin and clobetasol propionate was initiated. Upon admission, the patient presented with confluent erythematous lesions featuring pustules. It was assessed that the patient had experienced a flare of GPP, as evidenced by a GPPGA score of 3.
The patient was subfebrile and conveyed excessive skin pain combined with an increased heart rate, elevated C-reactive protein, an increased leukocyte, and neutrophilic count. The patient was hospitalized, treated with an infusion of 900 mg spesolimab and daily application of clobetasol propionate.
The day after infusion, the skin inflammation and the number of pustules were reduced, but increasing markers of infection alongside persistent subfebrile temperatures lead to initiation of antibiotic treatment. By day 3 following infusion, there were no pustules present on the skin.
Six days following spesolimab infusion, pustules were detected on the patient’s legs, but the patient described less skin pain. On day 7 after spesolimab administration, the number of pustules had vanished, resulting in a GPPGA score of 2, and the patient was discharged the next day.
At a 4-week follow-up, the patient reported sporadic use of clobetasol propionate, no side effects, or concurrent diseases. Objectively, there were patches with mild inflammation on the chest and lower back. Six weeks after spesolimab administration, an infection emerged from a leg wound. However, this infection did not result in a flare of his psoriasis. Subsequently, the patient was successfully treated with methotrexate and no side effects to spesolimab were reported (Fig. 1, 2).
The third patient, a 52-year-old male, had a history of von Zumbusch type of GPP and psoriatic arthritis. The patient had previously undergone a wide array of treatments, including methotrexate, acitretin, adalimumab, etanercept, golimumab, secukinumab, certolizumab pegol, apremilast, infliximab, brodalumab, and risankizumab (administered a week before admission). Upon admission, the patient had a severe GPP flare, presenting a GPPGA score of 4 upon admission, a normal leukocyte count combined with high levels of C-reactive protein.
Initial treatment consisted of potassium permanganate baths and topical corticosteroids followed by 900 mg spesolimab infusion on the third day. Five days post-spesolimab, the patient showed improvement with reduced erythema and absence of pustules. No side effects were reported. A week after spesolimab infusion the GPPGA score was 1, with no pustules, only mild scaling on the back, and residual erythema on previous lesions. Before discharge, the patient was prescribed acitretin.
At a 4-week follow-up after spesolimab treatment, the patient reported an area of pustules, which spontaneously resolved without further treatment. The skin displayed post-inflammatory hyperpigmentation and an extended degree of erythema.
Three months later, the patient only exhibited post-inflammatory hyperpigmentation. A year following spesolimab treatment, the patient commenced bimekizumab due to a flare in psoriasis vulgaris and joint pain. No side effects to spesolimab were reported (Fig. 2).
Discussion
Spesolimab is approved as monotherapy. However, in all three cases, topical treatment was given concomitantly probably due to tradition. Even though spesolimab was able to clear the pustules from the skin, all patients had highly inflamed skin and needed further treatments after a short period despite the use of topical steroids. The need for prevention of pustular flares is warranted especially for patients with von Zumbusch [6]. All patients demonstrated fast remission in their GPP. However, more observations in real-world cases are needed to evaluate the use of spesolimab in a real-world setting, which may be different from a trial population.
Acknowledgments
The authors acknowledge the invaluable contribution of the patients whose participation and willingness to share personal clinical information were essential to this study.
Statement of Ethics
This study was performed in accordance with the Declaration of Helsinki. Ethical approval was not received for this human study because the study was conducted in accordance with applicable national regulations, which do not require formal ethical approval for case reports involving anonymized patient data. All participants provided written informed consent to participate in this study. Written informed consent was obtained from the individuals for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000547428).
Conflict of Interest Statement
Boehringer Ingelheim provided the medication in response to requests for Named Patient Use. A separate grant to set up a patient database was provided by Boehringer Ingelheim. Boehringer Ingelheim was not involved in the development of the publication and did not contribute any scientific inputs to the publication. The authors have no conflict of interest to declare.
Funding Sources
Boehringer Ingelheim provided study medication and financial publication support.
Author Contributions
A.H.R., T.B., S.D.W.S., and L.I. contributed to the conceptualization and design of the study and were responsible for obtaining informed consent and collecting clinical data. A.H.R. drafted the initial version of the manuscript. All authors critically reviewed, revised, and approved the final version of the manuscript.
Funding Statement
Boehringer Ingelheim provided study medication and financial publication support.
Data Availability Statement
In accordance with the General Data Protection Regulation (GDPR) and institutional policies on patient confidentiality, the clinical data supporting this case series are not publicly available. The data consist of sensitive personal health information obtained with informed consent solely for the purpose of this publication. As such, further sharing is restricted to protect patient privacy. Further inquiries can be directed to the corresponding author.
Supplementary Material.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
In accordance with the General Data Protection Regulation (GDPR) and institutional policies on patient confidentiality, the clinical data supporting this case series are not publicly available. The data consist of sensitive personal health information obtained with informed consent solely for the purpose of this publication. As such, further sharing is restricted to protect patient privacy. Further inquiries can be directed to the corresponding author.