What data is available to support the off-label use of Opzelura (ruxolitinib) cream in pediatric patients with chronic skin graft vs host disease?

Background

A 2023 letter to the editor describes a retrospective study at a children’s medical hospital of pediatric patients with acute and chronic skin graft vs host disease (GVHD) treated with topical ruxolitinib. Clinical response in chronic GVHD was evaluated at 3 months or earlier depending on treatment resolution or intolerance. A total of 10 patients were included for analysis (median age 11.5 years), with 3 patients presenting with chronic GVHD. All 3 patients presented with maculopapular erythematous rash with a median day of chronic GVHD development post-transplant of 199 days (range 172 to 240 days) and all three patients had 3 or more prior systemic agents. Topical ruxolitinib cream was applied to the rashes, but not areas of sclerosis, for a median duration of 57 days. One patient was excluded from the results as they added a new systemic agent with topical treatment. The other two were evaluable, with the first patient achieving complete response at day 57 of treatment while the second patient achieved a partial response at day 34. The partial response patient had to terminate treatment due to pruritus. The complete response patient successfully ended treatment without requiring re-initiation or new topical agents. Additional adverse events included development of herpes simplex virus during treatment of an acute GVHD patient, but no organ toxicity or worsening of pre-existing viremia was observed, even when exceeding body surface area (BSA) application recommendations per package insert. Therefore, the limited findings suggest topical ruxolitinib to be well tolerated and potentially effective for pediatric and young adult patients. [1]

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What data is available to support the off-label use of Opzelura cream in pediatric patients with chronic skin graft vs host disease?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Table 1 for your response.

Topical Ruxolitinib for Chronic Cutaneous GvHD: Promising Results of a Phase 2 Clinical Trial
Design	Prospective, single-center, phase 2, randomized, double-blind trial N= 24
Objective	To evaluate the efficacy and safety of ruxolitinib 1.5% cream in patients ≥12 years old with cutaneous nonsclerotic (lichen planus-like, poikilodermatous) and superficially sclerotic (lichen sclerosus, morphea-like) chronic GvHD with ≥2% of body surface area (BSA) affected
Study Groups	Ruxolitinib (n= 12) Placebo (n= 12)
Inclusion Criteria	Stable use of systemic therapy for ≥4 weeks
Exclusion Criteria	Concurrent topical therapy or phototherapy
Methods	Patients were randomized 1:1 to ruxolitinib 1.5% cream to the left or right side of face/body with placebo vehicle cream to contralateral side twice daily over a period of 28 days.
Duration	June 28, 2019 to September 8, 2022 Treatment: 28 days
Outcome Measures	Primary: BSA of GvHD rash Secondary: Physician's Global Assessment (PGA), and Composite Assessment of Index Lesion Severity (CAILS) at days 14 and 28
Baseline Characteristics		Study cohort (N= 24)
	Age, years (range)	47.5 (18-78)
	Male	11 (46%)
	Medical history Acute leukemia Non-Hodgkin lymphoma	16 (67%) 4 (16%)
	Chronic GvHD Cutaneous nonsclerotic Lichen sclerosus-like	21 (87%) 3 (12.5%)
	Prior failed topical therapies Steroids Calcineurin inhibitors Phototherapy	88% 42% 29%
	Abbreviation: IQR= interquartile range Most patients were heavily pretreated, with a median of 2 prior systemic treatments and failure of ≥2 topical therapies. Patients with cutaneous nonsclerotic chronic GvHD were comprised of lichen planus-like (N=11), papulosquamous (N=7), and maculopapular rash/erythema features (N=3).
Results	Endpoint	Ruxolitinib (n= 12)	Placebo (n= 12)	p-value
	BSA of Chronic GvHD, % Day 1 Day 14 Day 28	14.4 7.7 6.2	14.5 10.4 10.4	0.12 0.002 0.003
	Both PGA and CAILS scores were significantly improved with treatment by day 14, and sustained to day 28; differences were significantly different between ruxolitinib and placebo.
Adverse Events	Common Adverse Events: 7 patients with 16 treatment-emergent adverse events; most common was orofacial dermatitis due to protective mask use (n= 2); one grade 1 headache potentially related to therapy
	Serious Adverse Events: N/A
	Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions	This is the first study to characterize the effect of topical JAK1/2 blockade on cutaneous cGVHD. Ruxolitinib 1.5% cream was safe and effective compared to placebo in treating cutaneous nonsclerotic and superficially sclerotic GvHD. Responders to ruxolitinib cream had genomic signature differences in IL-12 signaling from nonresponders. These encouraging results support a larger clinical trial to further evaluate the efficacy and safety of topical ruxolitinib in patients with cutaneous cGvHD.
InpharmD Researcher Critique	The full study is unavailable for scrutiny, and so findings should be considered with caution. Additionally, despite the inclusion of patients 12 years or older, all patients were adults. Use of systemic ruxolitinib in tandem with topical ruxolitinib was not addressed within the study, and so efficacy of combination therapy is uncertain.

References:

Markova A, Papadopoulos EB, Dusza S, et al. Topical Ruxolitinib for Chronic Cutaneous GvHD: Promising Results of a Phase 2 Clinical Trial. Blood. 2023;142(Suppl_1):777. doi:10.1182/blood-2023-182198