I have previously made the case that warts, both cutaneous and genital, are a relative contraindication to alemtuzumab therapy. I had one patient who has a torrid time with cutaneous warts after receiving alemtuzumab treatment. Fortunately, her immune system rejected them when it reconstituted and she is now fine.
At least with alemtuzumab and other IRTs (immune reconstitution therapies) you can rely on the immune system reconstituting; not so with continuous immunosuppressants.
I saw someone with MS yesterday who is on fingolimod with cutaneous warts, which are spreading, getting worse and causing a lot of discomfort. They were bleeding and were obviously causing her some distress. The bottom line is that the warts are unlikely to clear whilst she remains on fingolimod. Fingolimod is a drug that was repurposed from the solid-organ transplant field and is a chronic high-level immunosuppressant targeting both T and B cell responses of the immune system.
Warts on fingolimod is not a new problem; it is well described. In the case series below warts only responded to treatment and cleared when fingolimod was stopped. The problem is what to do about MS and MS rebound when you stop the fingolimod? In my opinion, the only solution is to go onto a DMT that is not a systemic immunosuppressive; these include interferon-beta, glatiramer acetate, teriflunomide and natalizumab. Another option is ocrelizumab as it selectively targets B-cells and leaves the T-cell compartment relatively intact, i.e. for the CD8+ cytotoxic T-cells to fight the viral infection that is causing warts.
The main problem we have in the NHS is the NHS England’s handcuffs in terms of eligibility for specific DMTs. This particular patient has previously failed the injectables so she is not going back onto those, she would not eligible for natalizumab as she does not have rapidly-evolving severe MS, which leaves only teriflunomide and ocrelizumab as viable options. The advantage of teriflunomide is that it is an oral agent, it has known antiviral effects and has a reversible mode of action. In comparison, ocrelizumab is a more effective DMT on average than teriflunomide, but as ocrelizumab is a depleting monoclonal antibody its action is irreversible. Ocrelizumab is also immunosuppressive and there is a definite herpes zoster signal with ocrelizumab, compared to interferon-beta and placebo. Ocrelizumab may, therefore, affect T-cell antiviral responses to HPV to some degree. Therefore based on a scientific rationale I would think the best agent for this patient is teriflunomide and if she is not keen on a de-escalation strategy, i.e. dropping down to a less effective agent, then she should switch to ocrelizumab. Do you agree?
She should also see a virologist to get the human papillomavirus causing warts genotyped. If this genotype is one that is covered by the polyvalent HPV vaccine (Gardasil-9) she may be able to receive this vaccine to boost her immunity to the virus once she is off fingolimod and on teriflunomide.
Triplett et al. Warts and all: Fingolimod and unusual HPV-associated lesions. Mult Scler. 2018 Nov 14:1352458518807088.
BACKGROUND: Fingolimod is used to reduce relapse rates in relapsing-remitting multiple sclerosis (MS). It is a sphingosine 1-phosphate (S1P) analogue having antagonistic effects on S1P receptors. Its immunosuppressive effect is due to reduced circulating lymphocyte numbers, and it may also be associated with impaired intrinsic cancer surveillance. Fingolimod side effects include increased rates and severity of viral infections particularly varicella zoster.
METHODS: We present five cases of chronic and treatment-refractory warts associated with fingolimod therapy.
RESULTS: Each of the five cases presenting with chronic warts while receiving fingolimod therapy had prolonged periods of lymphopenia and improvements were seen following dose reduction or cessation of fingolimod.
CONCLUSION: Cutaneous warts are associated with human papillomavirus (HPV) infection, suggesting an increased risk of other HPV-driven conditions such as cervical cancer following fingolimod administration. HPV viruses are responsible for approximately 90% of cervical cancers as well as a significant portion of anogenital cancers and have a high prevalence in sexually active adults. Given the reduced immune response to viral infections and potential impaired cancer surveillance in those receiving fingolimod, HPV vaccination and frequent assessment for the development of HPV-associated malignancies are recommended.
CoI: multiple
Will see siponimod have the same problems i.e. warts and also rebound?
Yes, almost certainly. It is a class effect all the S1P modulators are immunosuppressive.
I had hand warts when I was on Tecfidera. I’m not longer on Tec and they have gone now.
Not surprised; DMF is also an immunosuppressive and there is an increasing number of reports of opportunistic infections emerging from real-life experience.
I have (currently reasonably mild) RR MS. In February 2020 I had 3 verrucas treated ( 1 I had for many years!). By June they seemed to have almost gone but in August I started Tecfidera. By October two were back, bigger and more painful than before. By the time I was able to see a podiatrist one had developed an appearance the like of which she had never seen in her significant experience! It is the size of a 2p coin and bled like crazy when she started scraping it. Reading this and other articles makes me think that stopping/changing medication is the only way to guarantee getting rid of them!
Thanks for sharing this first hand case study.
I love those. They push us to think and educate us in the same time.
Why are warrants an issue with fingolimod an not Tysabri I am wondering? Is it simply down to a higher level of suppression?
Natalizumab (Tysabri) is not a systemic immunosuppressive; it selectively blocks trafficking of lymphocytes into the CNS and gut. We don’t see opportunistic infections outside of these sites. The problem is its label; rapidly-evolving severe MS.
That’s what I thought.
Reviving an old debate here, but how come many still call MS an auto-immune disease when higher levels of systemic suppression do not positively correlate with a lower ARR or slower BVL rate?
It is clearly not about immunosuppression, but something else. Could it be EBV?
That would imply that natalizumab is modulating EBV somehow…could that be possible?
“Vaccines are approved for use in males and females. They can only be used to prevent HPV infection – they don’t help treat an existing infection. To work best, the vaccines should be given at or before age 11 or 12.
https://www.cancer.org/cancer/cancer-causes/infectious-agents/hpv/hpv-and-cancer-info.html
Would it be safe, and potentially efficacious, to consider an innate immune system activator like imiquimod to treat the warts in such patients? It’s not licensed for cutaneous warts but has been tried off-licence I believe, including in immunocompromised patients, with some (not complete) success. https://www.ncbi.nlm.nih.gov/pubmed/25186654
Yes, and no! There is a UK case report of imiquimod reactivating MS in a patient who had been treated with alemtuzumab. We need to be careful with imiquimod in MS.
Hi, I have MS and have been treated with fingolimod for a few years. I have a lesion of skin and it has been recommended I use Imiquimod. I’m reluctant given my MS symptoms are extremely life limiting and painful especially when flared. I have little contact with my MS team due to staffing issues to discuss concerns. Do you have any thoughts? Any information would be so helpful, thank you.
Difficult. I am aware of one patient in Scotland who had warts treated with Imiquimod who had a major relapse. Imiquimod is a known immune stimulant and there is a chance that it may activate MS. Aggravation of MS is a listed adverse event:
https://www.rxlist.com/aldara-side-effects-drug-center.htm#overview
I suggest you discuss this with your neurologist and/or GP.
I’ve been on Gilenya for approximately 5 years and developed plantar warts on my toe approximately 1 year after starting. I’ve seen numerous dermatologists, podiatrists and have been receiving almost weekly treatments only for the lesions to spread and become more painful. I have asked my neurologist to assess this and possibly change my disease modifying therapy. I’m relieved to know that I’m not the only one this has happened to and found this article to be informative. I will be presenting it to my neuro at my next consult.