A small Australian study shows tofacitinib can be game changing to some patients with the severe chronic inflammatory condition.
Tofacitinib appears to be effective in the treatment of refractory erosive lichen planus (ELP), according to a small case series of 23 Australian women.
The 5mg twice daily oral dose improved disease severity and quality of life in patients with the vulvovaginal disease and led to complete resolution in those with oral disease.
This was an important, but underrecognised, condition with a lack of clear evidence guiding treatments, said study co-author and dermatologist Dr Rebecca Saunderson, visiting medical officer at the Prince of Wales Hospital.
“It has an incredibly detrimental impact on quality of life, so women who suffer with vulvovaginal lichen planus really have all domains of their life impacted,” she said.
“It often impacts their ability to perform at work. It impacts their personal relationships. They often can’t have penetrative intercourse, and that’s something that does impact their relationships, that has flow-on effects to how they feel about themselves and their self-confidence.”
Case reports on tofacitinib, a second-generation inhibitor of JAK1 and JAK3, have been promising in the treatment of this condition, which involves painful erosions and ulcers in mucosal sites.
To investigate further, the researchers analysed the patient database from a vulvovaginal sub-specialty clinic. Of the 23 adults with erosive vulvovaginal lichen planus (EVLP), six also had refractory oral ELP and one had oral and oesophageal ELP.
After treatment with the JAK inhibitor, 13% improved by two severity categories, half improved by one severity category and one in three reported symptom relief but hadn’t improved on the five-point Physician’s Global Assessment scale.
Symptom improvement took four months on average.
All patients with oral or oesophageal involvement achieved complete response after a mean of six months.
Women had almost a 12-point improvement, out of 45, on the Vulval Disease Quality of Life Index. Around 94% said their symptoms improved, 82% had better emotional wellbeing and 65% improved in daily activities.
More than half of the women who reported painful intercourse, dyspareunia, said they were able to return to pain-free sex.
Nevertheless, almost half of the patients reported mild side effects, and these included mild elevation of cholesterol, triglyceride and liver function tests, gastrointestinal discomfort, facial acneiform eruption and herpes zoster. Only one patient stopped treatment due to the gut discomfort.
One 68-year-old patient developed breast cancer, but the link to the JAK inhibitor was unclear.
This was a “very worthwhile” paper that should change clinical practice, said Clinical Associate Professor Kurt Gebauer OAM, a West Australian dermatologist who was not involved in the study.
Some dermatologists were wary following the black box warning on JAK inhibitors, but Professor Gebauer said many of his patients had become symptom-free, most with intermittent ongoing therapy.
“[JAK inhibitors] work extremely well on lichen planus of all sorts, and ulcerative lichen planus as a special need – and I think it’s important to get that message out,” he said.
“The side effect profile is pretty low compared to putting people on cyclosporin or methotrexate, et cetera.”
Dermatologist Professor Rod Sinclair, professor of medicine at the University of Melbourne, said this treatment would be “game changing for some”.
“These patients are difficult to treat, and so if you can actually access that medication and you have a patient with severe disease who was refractory to everything else, you would probably give it a try.”
Dr Saunderson said some patients could get the drug via a compassionate access. Some dermatologists report getting the medicine compounded off-label.
Professor Sinclair said generic versions of tofacitinib may soon become available as the drug goes off patent in the next few years, “so there will be greater opportunity to use it when it becomes more accessible and less costly”.
-
Atopic Dermatitis Biologics safe and effective for young patients... -
Biologic Treatments Used in Dermatology Why do psoriasis patients switch biologics? -
Biologic Treatments Used in Dermatology Genes predict the best biologics for psoriasis
More research was currently under way into JAK inhibitors, including baricitinib, to determine whether others in the class were even more effective at treating this condition.
Dr Saunderson and colleagues are currently recruiting patients for a randomised controlled trial on the TYK2 inhibitor deucravacitinib, and clinicians can find out more at drummoyne@dermatology.com.au.
In the current study, the mean age at diagnosis was around 48 years and mean follow-up duration was almost six years. Less than half of these patients had biopsy features suggestive of EVLP and the rest met the diagnostic criteria.
Dr Saunderson and colleagues noted that up to 40% of erosive vulvovaginal lichen planus cases did not respond to first-line topical corticosteroid therapy, and required systemic agents.
This highlighted the need for more targeted therapies to address the varying efficacy and side effects of other immunosuppressive medications such as methotrexate and prednisolone, they wrote.
