Treatment of Severe Palmoplantar Pustular Psoriasis With Bimekizumab

This case series describes the use of bimekizumab for the treatment of palmoplantar pustulosis and palmoplantar plaque psoriasis with pustules.

Key Points

Question

Is bimekizumab effective in treating palmoplantar pustulosis (PPP) and palmoplantar plaque psoriasis with pustules?

Findings

In this multicenter case series of 21 patients with PPP or palmoplantar plaque psoriasis with pustules treated with bimekizumab for at least 3 months, 17 patients showed complete clearance (Investigator Global Assessment [IGA] score of 0) in 1 to 4 months, 3 patients had an IGA score of 1 (almost clear), and 1 had an IGA score of 2 (mild). Two patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome had complete clearance of skin lesions and improvement in joint pain.

Meaning

Findings of this case series suggest that bimekizumab may be effective for treating PPP, palmoplantar plaque psoriasis with pustules, and SAPHO syndrome.

Abstract

Importance

Palmoplantar pustulosis (PPP) and palmoplantar plaque psoriasis with pustules remain challenging to treat. Studies suggest that an interleukin 17 or interleukin 36 loop acts synergistically in these diseases to induce palmoplantar pustules.

Objective

To assess the effectiveness of bimekizumab in treating PPP and palmoplantar plaque psoriasis with pustules.

Design, Setting, and Participants

This case series involved 21 adults with PPP (11 patients) or palmoplantar plaque psoriasis with pustules (10 patients) treated at 1 of 7 tertiary dermatological centers in France from September 2022 through June 2023. All patients treated with bimekizumab for at least 3 months were included in the analyses.

Main Outcomes and Measures

The main outcome was the posttreatment Investigator Global Assessment (IGA), scored as 0 (complete clearance), 1 (almost clear), 2 (mild), 3 (moderate), or 4 (severe). When relevant, evolution of joint pain and nail involvement was reported. Tolerance and potential adverse events were noted.

Results

A total of 21 patients (mean [range] age, 46 [24-68] years; 19 females) were included. Eleven patients had isolated PPP, and 10 had palmoplantar plaque psoriasis with pustules. All of them, except 2 who received bimekizumab as first systemic therapy, had not responded to at least 1 systemic treatment (median [range], 3 [1-7] treatments), and/or had adverse events leading to the discontinuation of the treatment. Complete clearance (IGA score, 0) was achieved by 17 patients in 1 to 4 months. Three patients achieved an IGA score of 1, and 1 achieved an IGA score of 2. Three patients with PPP also presented with acrodermatitis continua of Hallopeau. Nail involvement showed 50% to 70% improvement after 4 to 6 months of bimekizumab treatment for these 3 patients. Two patients had SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome; both had complete clearance of skin lesions associated with joint pain improvement. Four patients (19%) with candidiasis were successfully treated with oral antifungal agents. None of the patients had to stop bimekizumab treatment due to adverse events.

Conclusions and Relevance

The findings of this case series suggest that bimekizumab could be an appealing approach for treating PPP, palmoplantar plaque psoriasis with pustules, and SAPHO syndrome. Prospective randomized placebo-controlled clinical trials are needed to confirm these encouraging initial results.

Introduction

Among the types of localized pustular psoriasis, palmoplantar pustulosis (PPP) is defined as primary, persistent (>3 months), sterile, macroscopically visible pustules on palms or soles that can occur with or without psoriasis vulgaris according to the ERASPEN Network consensus statement.¹ The lesions, which can occur on a background of normal or inflamed skin, are painful and disabling and can be accompanied by fissures, pruritus, and a burning sensation that can profoundly affect the patient’s quality of life. The term PPP has been applied to several entities, suggesting heterogeneous underlying pathophysiological pathways. In some cases, PPP is associated with bone and joint inflammation in SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Additionally, palmoplantar plaque psoriasis with pustules is a localized plaque psoriasis with the co-occurrence of pustules. In addition to this heterogeneity, there is continuing controversy over whether PPP is a localized form of pustular psoriasis or a psoriasis-related disease.

The immune pathways that underlie the pathogenesis of PPP remain unclear. IL36RN gene sequence alterations, which underlie the pathogenesis of psoriasis-related pustular eruptions, are seen in patients with palmoplantar plaque psoriasis with pustules with a predominance of hypomorphical sequence alterations, suggesting a possible correlation between genotype and clinical phenotype.² However, the frequency of IL36RN, CARD14, and AP1S3 sequence alterations is much lower in PPP than in generalized pustular psoriasis (GPP), supporting the idea that PPP is not a localized variant of GPP. Recent data with spesolimab (an anti–interleukin [IL]–36 monoclonal antibody) showing marked improvement in GPP,³ but not in PPP,⁴ further support that IL-36 is not the main factor in PPP. Additionally, rather than being a monogenic inflammatory disease, PPP has substantial genetic heterogeneity and remains poorly understood at the genetic level.

Available treatments for PPP and palmoplantar plaque psoriasis with pustules remain unsatisfactory, likely because multiple immune pathways are simultaneously activated in these conditions. Acitretin can be of some help in some patients and remains for many physicians the first systemic approach. Cyclosporine remains the best option available, but it is not always effective and tolerance is often poor, with frequent and sometimes severe adverse events that often prevent its long-term use. Available biologic agents, including anti–tumor necrosis factor, anti–IL-12, anti–IL-17A, and anti–IL-23, improve disease in approximately one-third of patients with PPP; thus, the disease remains a therapeutic challenge.⁵ Bimekizumab is an anti–IL-17A and anti–IL-17F antibody therapy that has been useful for treating psoriasis and psoriatic arthritis.^6,7 Some preliminary data suggest that bimekizumab reduces IL-36 levels in the serum by simultaneously blocking IL-17A and IL-17F.⁸ These data suggest that bimekizumab could be an appealing option for treating PPP and palmoplantar plaque psoriasis with pustules through the inhibition of various pathways. The aim of the present study was to assess the effectiveness of bimekizumab for management of PPP and palmoplantar plaque psoriasis with pustules.

Methods

A case series that included adults with PPP or palmoplantar plaque psoriasis with pustules was conducted from September 2022 through June 2023 in 7 tertiary dermatological centers in France. The Centre Hospitalier Universitaire de Nice ethics board deemed this study exempt and waived the informed consent requirement because of its observational nature and the absence of nominative information. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

All patients with PPP or palmoplantar plaque psoriasis with pustules who were treated for at least 3 months with bimekizumab were included in analyses. The main outcome was the Investigator Global Assessment (IGA), scored as 0 (complete clearance), 1 (almost clear), 2 (mild), 3 (moderate), or 4 (severe). When relevant, the evolution of joint pain and nail involvement was reported. Drug tolerance and potential adverse events were also noted.

Results

Between September 2022 and June 2023, 21 patients were identified (mean [range] age, 46 [24-68] years; 19 females (90%) and 2 males [10%]). Eleven patients had isolated PPP, and for 10 patients the palmoplantar pustular lesions were associated with plaque psoriasis on the body (ie, palmoplantar plaque psoriasis with pustules). Demographic characteristics, previous treatments, and disease evolution with bimekizumab for each patient are summarized in the Table. Two patients received bimekizumab as initial systemic therapy; the remaining 19 patients did not respond to at least 1 systemic treatment (median [range], 3 [1-7] treatments) or had adverse events leading to the discontinuation of the initial treatment. Most of the patients started to improve between 15 to 30 days after the initiation of bimekizumab. Complete clearance (IGA score, 0) was achieved by 17 patients in 1 to 4 months (Figure). Three patients achieved an IGA score of 1, and 1 achieved an IGA score of 2 over 3 to 6 months.

Table. Demographic Characteristics and Treatment Course of 21 Patients With Palmoplantar Pustulosis, SAPHO Syndrome, or Palmoplantar Plaque Psoriasis With Pustules Treated With Bimekizumab.

Patient sex	Patient age, y	Association with plaque psoriasis?	Psoriatic arthritis?	Previous therapies	Duration of bimekizumab treatment, mo	Clinical evolution under bimekizumaba	BSA involvement before and after bimekizumabb	Adverse events
F	40s	No	Yes	Methotrexate, adalimumab, acitretin, secukinumab, ixekizumab, rizankizumab	9	First improvement after 2 wk; IGA score 0 at 4 mo	NA	None reported
F	60s	No	No	Methotrexate, acitretin, cyclosporine, adalimumab, ixekizumab, brodalumab, rizankizumab	9	Complete clearance after 4 mo; IGA score 0 at 6 mo	NA	None reported
F	50s	Yes	No	PUVA therapy, acitretin, etanercept, tildrakizumab	8	Complete clearance after 2 wk; IGA score 0 at 6 mo	3%/0%	Transient oral candidiasis, headache, site injection reaction
F	50s	No	No	Acitretin, methotrexate, apremilast, spesolimab	7	Complete clearance after 2 wk; IGA score 0 at 6 mo	NA	Transient oral and genital candidiasis
F	60s	Yes	No	Methotrexate, acitretin, cyclosporine, ustekinumab, ixekizumab, brodalumab, guselkumab	8	Initial worsening after stopping cyclosporine followed by progressive improvement; IGA score 2 at 6 mo	10%/0%	Folliculitis, mild eczematous lesions
F	30s	No	Yes	Methotrexate, ustekinumab, ixekizumab, adalimumab	9	Complete clearance after 4 mo; IGA score 0 at 6 mo; >70% improvement of Hallopeau disease; no more joint pain	NA	Transient oral and genital candidiasis
F	30s	No	No	Secukinumab	8	IGA score 0 at 3 mo	NA	None reported
F	40s	Yes	No	Guselkumab	3	IGA score 0 at 3 mo	12%/0%	None reported
F	50s	No	No	Methotrexate, acitretinin	6	Complete clearance after 4 mo; IGA score 0 at 6 mo; >70% improvement of Hallopeau disease	NA	None reported
F	30s	Yes	Still diseasec	Methotrexate, infliximab	6	Complete clearance after 3 mo; IGA score 0 at 3 mo	9%/0%	None reported
F	20s	Yes	SAPHO syndrome	Secukinumab	6	First improvement after 2 wk; IGA score 0 at 4 mo; clearance of bipolar aphthosis and no more join pain	3%/0%	None reported
F	40s	Yes	Yes	Certolizumab pegol, secukinumab, guselkumab, infliximab, ixekizumab	6	First improvement after 1 mo; IGA score 1 at 3 mo; no more join pain	10%/3%	None reported
F	30s	Yes	No	Methotrexate	5	Complete clearance after 6 wk; IGA score 0 at 6 mo	80%/3%	None reported
F	40s	Yes	Yes	Certolizumab pegol, secukinumab, infliximab, ixekizumab	3	Complete clearance after 3 mo; IGA score 1 at 6 mo	10%/3%	None reported
M	50s	Yes	No	PUVA therapy, methotrexate	4	IGA score 0 at 3 mo	20%/0%	None reported
F	40s	No	No	Topical steroids	3	Complete clearance after 2 wk; IGA score 0 at 3 mo	NA	None reported
F	50s	No	SAPHO syndrome	Topical steroids	4	Complete clearance after 2 wk; IGA score 0 at 3 mo	NA	None reported
M	30s	Yes	No	Acitretin, apremilast, UV-B, rizankizumab	6	Complete clearance after 2 wk; IGA score 0 at 3 mo	10%/0%	None reported
F	50s	No	No	Methotrexate, ustekinumab, guselkumab, secukinumab, risankizumab	6	Complete clearance after 3 wk; IGA score 0 at 6 mo	NA	None reported
F	40s	No	Yes	Ixekizumab	7	IGA score 1 at 6 mo 50% improvement of Hallopeau disease	NA	Transient oral candidiasis
F	60s	No	No	Methotrexate, guselkumab, risankizumab	4	Complete clearance after 2 wk; IGA score 0 at 3 mo	NA	None reported

Abbreviation: BSA, body surface area; F, female; IGA, Investigator Global Assessment; M, male; NA, not applicable; PUVA, psoralen UV-A light; SAPHO, synovitis, acne, pustulosis, hyperostosis, and osteitis.

^a The IGA scale ranking is as follows: 0 (complete clearance), 1 (almost clear), 2 (mild), 3 (moderate), or 4 (severe).

^b Results presented only for patients with associated plaque psoriasis.

^c A chronic inflammatory disease.

Figure. Clinical Features Before and After Treatment With Bimekizumab in a Patient With Palmoplantar Pustulosis (PPP) and Acrodermatitis Continua of Hallopeau and in a Patient With PPP.

Three patients with PPP also presented with acrodermatitis continua of Hallopeau. In these 3 patients, nail involvement showed 50% to 70% improvement after 4 to 6 months of bimekizumab. Additionally, 2 patients presented with SAPHO syndrome. The first patient with SAPHO syndrome started improving after 1 month of bimekizumab treatment, and skin lesions cleared at 4 months. This patient’s joint pain and bipolar aphthosis also cleared within 4 months. The second patient with SAPHO syndrome had a partial response after 6 months of secukinumab and was then switched to bimekizumab, achieving complete clearance in 1 month. This patient’s joint pain was already improved while taking secukinumab, and pain control did not change after switching to bimekizumab.

Drug tolerance was good. During treatment, 4 patients (19%) developed oral and genital candidiasis that was successfully treated with oral fluconazole. None of the patients had to stop bimekizumab treatment due to adverse events. All patients are still receiving treatment, and their psoriatic lesions remain controlled.

Discussion

Although the effectiveness of bimekizumab for management of psoriasis vulgaris has been described, data are lacking about the drug’s potential effectiveness in managing PPP and palmoplantar plaque psoriasis with pustules. The rapid and consistent improvement observed in the present case series supports the effectiveness of bimekizumab therapy in managing PPP, palmoplantar plaque psoriasis with pustules, and SAPHO syndrome. Other than isolated case reports, data on the use of anti–IL-17 agents used to manage PPP are limited. To our knowledge, the only multicenter prospective randomized trial⁹ on PPP used secukinumab and did not meet its primary end point. In that study, the primary end point (a 75% improvement from baseline in the Palmoplantar Psoriasis Area and Severity Index at week 16) was achieved in 26.6% of patients receiving secukinumab, 300 mg, at week 16 (vs 14.1% of patients receiving placebo) and in 41.8% of patients taking the drug at week 52.⁹ These results suggest some effectiveness of anti–IL-17A antibodies in treating PPP, but they also show the limitations of targeting only this cytokine in this specific form of psoriasis. Immunological studies have found increased IL-17 and IL-22 levels in the serum and lesions of patients with PPP¹⁰ along with increased circulating T helper 17 (T_H17) cells.¹¹ Transcriptional studies¹² found that the transcriptome patterns of PPP and palmoplantar plaque psoriasis with pustules are strikingly similar, suggesting that the 2 diseases are a single entity that differ in their clinical phenotype. Comparison of the gene expression of PPP and normal acral skin showed an increase in activation of the T_H17 axis with an increase in IL-17 gene expression (but without an increase in IL-23 activation) and activation of T helper 1 (T_H1) cells. Levels of IL-36β/γ and IL-36 receptor antagonist are increased in normal acral skin, and levels of IL-36γ are further increased in palmoplantar plaque psoriasis with pustules and in PPP.¹² Upregulation of IL-36 in acral skin may therefore play a role in the predilection of pustular psoriasis on palms and soles. Interleukin-17 cytokines are strong inducers of keratinocyte hyperproliferation, which results in upregulation of keratinocyte-derived proteins such as the S100 proteins, chemokines (CXCL1/2/3/5/8 and CCL20), other antimicrobial peptides, IL-17C, and IL-36 isoforms.^13,14 Resulting IL-36 upregulation (in response to IL-17A and IL-17F as well as IL-17C from keratinocytes) signals in an autocrine fashion to further induce its own upregulation, and T_H17 cytokines act synergistically with IL-36 to further promote activation of the IL-23/IL-17 axis.^13,14,15 Altogether, these data suggest that disrupting the IL-17/IL-36 loop may be useful for treating PPP and palmoplantar plaque psoriasis with pustules. In 1 study,¹⁶ neutralization of IL-17A and IL-17F with bimekizumab provided greater suppression of in vitro cytokine responses and neutrophil chemotaxis than inhibition of IL-17A or IL-17F alone.

Limitations

The main limitations of this study are the small number of patients and the relatively short follow-up under bimekizumab treatment. Additionally, because of the severity of their disease, most patients were resistant to at least 1 line of therapy, and thus we may have selected the most difficult cases.

Conclusions

The results of this case series suggest that bimekizumab could be an appealing approach for treating PPP, palmoplantar plaque psoriasis with pustules, and SAPHO syndrome. A prospective placebo-controlled randomized clinical trial is warranted to confirm these encouraging initial results.

Supplement.

Data Sharing Statement