Ruxolitinib cream has significantly reduced lesions and itch in patients with cutaneous lichen planus, raising the prospect of a nonsteroidal treatment for the notoriously stubborn condition.
A topical JAK inhibitor has significantly improved lesions and itch in adults with cutaneous lichen planus, including patients previously treated with potent topical corticosteroids.
Ruxolitinib 1.5% cream was associated with four-fold higher odds of achieving treatment success compared with vehicle after 16 weeks, according to a phase 2 randomised trial published in JAMA Dermatology.
The findings address a sizeable therapeutic gap. Cutaneous lichen planus affects an estimated 0.2% to 1% of adults and can cause intense pruritus, pain, and visible lesions that impair quality of life. There are currently no disease-specific approved therapies, according to the team behind the new research.
Potent topical corticosteroids are often used first line despite limited evidence from large, controlled trials and the potential for adverse effects. Refractory disease is common, leaving treatment choices frequently driven by clinician experience and trial and error.
“Despite available treatments, LP often proves to be recalcitrant,” the researchers wrote.
“In the present study, ruxolitinib cream quickly and substantially reduced signs and symptoms, including a statistically significant itch reduction vs the vehicle; thus, it may represent an alternative treatment for cutaneous lesions in some patients.
“Adverse reactions associated with topical corticosteroids can be avoided with the use of nonsteroidal alternatives, such as ruxolitinib cream.”
Ruxolitinib inhibits JAK1 and JAK2, pathways thought to play an important role in lichen planus inflammation. Interferon-gamma and some type I interferons are believed to promote keratinocyte changes leading to CD8-positive T-cell-mediated cytotoxicity, with JAK-dependent signalling and downstream STAT1 activation implicated in the process.
The trial included 64 adults from 19 centres in the US and Canada with predominantly cutaneous lichen planus. Patients had moderate or severe disease, an itch score of at least four and affected body surface area ≤20%.
They were randomised to ruxolitinib 1.5% cream or matching vehicle twice daily for 16 weeks, followed by a 16-week open-label extension in which eligible patients used ruxolitinib twice daily as needed.
Participants had a median age of 57 years and 72% were women. Median disease duration was 4.9 years and 91% had previously received treatment for lichen planus.
Almost half had hypertrophic lichen planus, one of the more persistent forms. Mean baseline itch and skin pain scores were 6.5 and 4.7 respectively, while two-thirds of participants had biopsy-confirmed disease.
The primary endpoint was Investigator’s Global Assessment treatment success, defined as clear or almost clear skin combined with an improvement of at least two grades from baseline.
At week 16, 50% of patients receiving ruxolitinib reached that endpoint compared with 21.9% receiving vehicle, a response-rate difference of 29.4 percentage points. The odds ratio was 4.0 (95% CI 1.3-12.4), with improvement apparent from week four.
Among patients with observed data, 30% of the ruxolitinib group had completely clear skin at week 16 and 23.3% were almost clear, compared with 3.4% and 20.7% respectively in the vehicle arm.
Improvement continued during the extension. Among patients initially assigned to ruxolitinib, treatment success increased from 53.3% at week 16 to 60% at week 32. Patients who crossed from vehicle to active treatment also improved, with 60.9% of those assessed reaching treatment success at week 32.
Itch also responded quickly. At week 16, 48.4% of patients receiving ruxolitinib achieved at least a four-point improvement in itch compared with 16.1% receiving vehicle, producing an odds ratio of 5.5 (95% CI 1.6-18.7).
Median time to that degree of improvement was 17 days with ruxolitinib compared with 97 days with vehicle. Among evaluable patients who received ruxolitinib from the outset, the proportion achieving the itch endpoint rose to 84.2% by week 32.
Related
Pain also fell, with a mean three-point reduction in skin pain at week 16 with ruxolitinib compared with 1.3 points for vehicle. By week 32, the reduction among evaluable patients originally assigned to ruxolitinib reached 4.3 points.
Affected body surface area began declining by week two. At week 16, the mean reduction was 2.7 percentage points with ruxolitinib compared with 0.2 percentage points with vehicle.
The results were notable given 91% of participants had received previous lichen planus treatment. The most common medication classes used in the previous year included very potent, moderately potent, and potent topical corticosteroids.
Treatment-emergent adverse events occurred in 48% of ruxolitinib-treated patients during the double-blind period compared with 28% receiving vehicle. Three events were considered treatment related: application-site folliculitis, covid, and insomnia.
But there were no serious treatment-emergent adverse events with ruxolitinib and none led to treatment discontinuation. There were also no deaths, major adverse cardiovascular events, thromboses, or serious infections during the study.
One patient who crossed from vehicle to ruxolitinib developed squamous cell carcinoma. The lesion occurred outside the treatment area and was judged by the investigator to be unrelated to the study drug.
The researchers said the findings supported JAK1/JAK2 inhibition as a potential way of targeting key elements of lichen planus pathophysiology and suggested ruxolitinib could provide a nonsteroidal alternative for some patients.
But they cautioned that the trial was small and the modified IGA used for the primary endpoint has not been formally validated. Around one-third of participants lacked biopsy confirmation, while the large proportion with hypertrophic lichen planus may limit generalisability to other variants.
“Phase 3 studies are needed to confirm these data in a larger population,” the researchers wrote.
Despite this, the trial dd show significantly reduced LP lesions and itch.
“Substantially reduced pain vs the vehicle, with rapid onset of effects, was observed,” the researchers concluded.
“Therefore, ruxolitinib cream represents a promising potential treatment for cutaneous LP.”
