Skin warts during fingolimod treatment in patients with multiple sclerosis

Jaafar, Nesreen; Zeineddine, Maya; Massouh, Joelle; Yamout, Bassem

doi:10.1016/j.msard.2019.101437

Cited by 10 publications

(5 citation statements)

References 7 publications

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“…These cases highlight the previously reported problem of treatment-refractory warts in patients taking fingolimod for MS 4–6. We retrospectively identified warts in 7 out of 336 patients (2.1%) receiving fingolimod at our centre between 2011 and 2019.…”

Section: Casementioning

confidence: 74%

“…Both cases highlight treatment refractory warts in patients on fingolimod for MS, as previously reported. [4][5][6] We retrospectively identified warts in 7/336 patients (2.1%) receiving fingolimod at our centre between 2011-2019. Treatment was modified in four patients; Two patients discontinued fingolimod with either improvement or resolution, although one subsequently relapsed.…”

mentioning

confidence: 99%

“…[7,8] Causality between fingolimod and warts remains unproven, but is supported by the temporal relationship between treatment modification and improvement in warts. [4][5][6] Fingolimod may impair the immune response to HPV through lymphocyte sequestration, mediated by sphingosine-1-phosphate (S1P) receptor antagonism, and cause warts through chronic infection and clonal proliferation of keratinocytes. Fingolimod may also increase the risk of HPV-driven malignancy [1,6] through impaired T-cell mediated cancer surveillance.…”

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confidence: 99%

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Treatment-refractory warts associated with fingolimod

et al. 2022

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Case 1 -(Figure 1a) A 54-year-old woman with relapsing remitting multiple sclerosis (RRMS) on fingolimod since 2018 presented with periungual digital warts. She had previously switched from Natalizumab, due to JC virus seropositivity, and had relapsed on interferon beta-1a. Although her warts persisted despite topical treatment with salicylic acid, she wished to continue fingolimod therapy.Case 2 -(Figure 1b) A 54-year-old woman with RRMS) commenced fingolimod in 2014, following relapse on interferon beta-1a. She developed digital warts in 2016, which became widespread despite treatment with salicylic acid and cryotherapy. Warts improved following dose reduction in 2019 but remained persistent.Cutaneous warts are caused by the human papilloma virus (HPV).[1,2] Prevalence varies markedly in studies, but is highest during childhood (~5-30%) and falls significantly following the second decade of life.[1,2] Salicylic acid or cryotherapy are the most evidenced treatments with cure rates around 50%, but multiple therapies exist and spontaneous resolution is common.[1] However, in the immunocompromised, warts are often refractory to standard treatments[1] with significant psychosocial impact.

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Section: Casementioning

confidence: 74%

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confidence: 99%

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confidence: 99%

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Treatment-refractory warts associated with fingolimod

et al. 2022

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“…Annual HPV screening is only recommended in alemtuzumab-treated MS patients, a similar approach to recommended screening in HIV patients. HPV-related benign lesions and cancers are increasingly reported in fingolimod-treated patients, suggesting an increased incidence of skin and mucosal warts with fingolimod [ 54 , 55 ], the majority being HPV-related cervical dysplasia in female patients and one unique case of HPV-related papillary squamous cell carcinoma of the tonsil in male patient [ 56 ]. Screening for HPV and cervical cancer is not typically performed as part as routine testing for patient on fingolimod.…”

Section: Monitoring Of Adverse Eventsmentioning

confidence: 99%

Safety of Newer Disease Modifying Therapies in Multiple Sclerosis

et al. 2020

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In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab), and are associated with better control of disease activity and long-term outcomes in patients with MS compared to older injectable therapies (interferon beta and glatiramer acetate). However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach.

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“…Five other recent cases of benign warts on fingolimod have also recently been reported separately. 7 The temporal relationship between treatment discontinuation and lesion improvement support a possible causal role for fingolimod and an increased susceptibility to HPV infections. Moreover, viral-associated malignancies on fingolimod have been reported, with five cases of HPV-related vulvar and cervical dysplasia and a case of HPV16-related squamous cell carcinoma of the tonsils.…”

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confidence: 92%

Clinical commentary on “Warts and all: Fingolimod and unusual HPV associated lesions”

Macaron

Ontaneda

2018

Mult Scler

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TEVA. Additional interests and potential conflicts of interest include the following: co-founder/shareholder of Medical Safety Systems (grant and contracts with Genzyme >AUD$25,000 including a per patient payment, potential application to multiple drugs); National IVIG Governance Advisory Council & Specialist Working Group Australia (Neurology) (paid); Australian Technical Advisory Group on Immunisation Varicella Zoster working party (unpaid); Nerve Research Foundation board member (unpaid); Public Salary as a staff specialist neurologist from Sydney Local Health District (paid); Private billings from patients and Medicare Australia reimbursement as a private practice neurologist (paid); and Medical advisor (unpaid) to various patient and advocacy groups.

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Skin warts during fingolimod treatment in patients with multiple sclerosis

Cited by 10 publications

References 7 publications

Treatment-refractory warts associated with fingolimod

Treatment-refractory warts associated with fingolimod

Safety of Newer Disease Modifying Therapies in Multiple Sclerosis

Clinical commentary on “Warts and all: Fingolimod and unusual HPV associated lesions”

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