The goals of therapy for atopic dermatitis include reducing symptoms of pruritis and dermatitis with disease control and prevention of flares.
RR is a 22-year-old female patient presenting to the dermatology clinic. She has a past medical history significant for atopic dermatitis (AD) and eczema.
She was treated with steroids in childhood but stopped taking them in 2019. Her eczema was controlled while she was treated with narrow-band ultraviolet B (NB-UVB) therapy; however, she discontinued treatments due to her work schedule.
RR currently presents with severe eczema, body surface area (BSA) of 75%, involving the hands and feet, and her back is the clearest part of her body. She reports that when she scratches, her legs start to weep. She presents with dry and scaly skin.
Her current treatments for AD include a moisturizing advance repair cream, ammonium lactate cream 12%, cephalexin 500 mg, dupilumab injection 300 mg/2ml, and ruxolitinib 1.5% cream for stubborn areas around her neck. RR is unable to sleep at night due to severe itching and is on hydroxyzine as needed. She was on a course on chlorthalidone for 2 weeks for edema.
Her provider has recommended she avoid products and soaps with fragrance as well as long warm showers. She has seen some improvement since starting dupilumab injections but is still experiencing shedding and itching.
She has no family history of psoriasis and reports her father and paternal grandmother had severe eczema. The physician decides to initiate RR on upadacitinib, a Janus kinase (JAK) inhibitor.
The physician wants her to continue her current medication regimen for AD, including dupilumab injections. She is advised to get vaccinated against the zoster virus.
The prescriber sends a prescription for upadacitinib to the specialty pharmacy for processing and delivery. During the clinical review, the pharmacist notes an interaction between upadacitinib and ruxolitinib cream.
What should the pharmacist recommend for RR’s treatment?
Labs from today’s visit
AD is a chronic, inflammatory skin condition characterized by skin dryness, erythema, oozing, crusting, and lichenification (thickened and leathery skin). The strongest risk factor for AD is family history of the disease.
The presence of AD in one parent increases a child’s risk of developing AD by 1.5-fold, with a 3- to 5-fold increase when both parents have AD.1 The goals of therapy for AD include reduction in symptoms of pruritis and dermatitis with disease control and prevention of flares. Patients with moderate to severe disease are treated with systemic therapies.
Upadacitinib and ruxolitinib are both JAK inhibitors.2,3 Ruxolitinib selectively inhibits JAK1 and JAK2—protein tyrosine kinases involved in signaling of cytokines and growth factors.
In September 2021, the FDA approved a topical formulation of ruxolitinib for mild to moderate AD in non-immunocompromised adult and pediatric patients 12 years of age and older. The manufacturer recommends instructing patients to apply ruxolitinib cream to the affected area up to 20% of BSA.2
Upadacitinib is approved for the treatment of moderate to severe AD, not adequately controlled with other systemic drugs in pediatric patients 12 years of age and older and in adults.3 The manufacturer of ruxolitinib and upadacitinib recommend not using the medication in combination with another JAK inhibitor, therapeutic biologics, or potent immunosuppressants.2,3
RR’s symptoms and presentation are consistent with a severe form of AD and the labs are within range. The physician was informed about the manufacturer recommendations on avoiding concomitant JAK inhibitor administration with upadacitinib.
Subsequently, the order for ruxolitinib cream was discontinued. RR will continue to administer dupilumab injections and initiate oral upadacitinib tablets.
Patients with AD need optimal skin hydration and moisturization for atopic itch management. RR will continue the OTC moisturizing repair cream twice daily, applying thick coatings after showers.
She should continue to apply ammonium lactate cream twice daily on dry skin along the neck, upper and lower extremities. RR is also at risk for cutaneous bacterial, viral or fungal infections. She will complete the 7-day course of cephalexin to treat the lesions.
A clinical trial conducted by Gong et. al examined the pharmacokinetics of ruxolitinib cream in patients with AD.4 The phase 2 and 3 studies were performed with different concentrations of ruxolitinib cream with once- or twice-daily frequency.
The study examined the pharmacokinetic effect at baseline, plasma concentrations, and any changes in hematological parameters over time. The researchers concluded that plasma concentrations were minimal after treatment with topical ruxolitinib in patients with 20% BSA affected by AD.
Although plasma concentrations are minimal after the topical application of ruxolitinib cream, further studies are required to evaluate the safety of the topical formulation with an oral JAK inhibitor. The recommended upadacitinib dose for pediatric patients 12 years of age and older weighing at least 40 kg and adults less than 65 years of age is 15 mg orally once daily.3
Providers may increase the dose to 30 mg orally once daily on inadequate response. For adults older than 65 years of age, the recommended dosage is 15 mg orally once daily.
Upadacitinib may increase the risk of cardiovascular events, deep vein thrombosis, malignancies, and intestinal perforation. Women of childbearing age should use an effective form of birth control to avoid pregnancy during treatment and for 4 weeks after the last dose.
Upadacitinib may pass into the breast milk, women should be counseled to avoid breastfeeding during treatment and for 6 days after the last dose. Patients should be reminded to complete their blood work on time.
Prior to initiating upadacitinib, patients must be up to date on all immunizations, including varicella zoster or prophylactic herpes zoster vaccination. Health care providers must avoid administration of live vaccines during or immediately prior to initiating upadacitinib therapy in patients.
About the Authors
Rumla Rizvi, PharmD, MS, is a specialty clinical pharmacist working in inflammatory diseases at the Outpatient Pharmacy Services.
Bisni Narayanan, PharmD, MS, is the supervisor for operations at the Outpatient Pharmacy Services. Outpatient Pharmacy Services is a specialty pharmacy integrated within the Yale New Health System.