Why Some Dermatologists Are Adopting JAKs for Uncontrolled Moderate-to-Severe Atopic Dermatitis

Sponsored by Pfizer

Managing atopic dermatitis (AD), also known as eczema, remains a significant challenge for many patients and dermatologists. Despite the use of topical agents and systemic treatments such as biologics, many patients still experience uncontrolled symptoms like persistent itching and discolored, scaly skin.^1,2 

In recent years, an innovative class of treatments called Janus kinase inhibitors (JAKs) have emerged as an option for patients with refractory moderate-to-severe AD whose disease is not adequately controlled with other systemic drugs or who cannot use those therapies.³

Peter Lio, MD, a dermatologist at Medical Dermatology Associates of Chicago and Clinical Assistant Professor of Dermatology and Pediatrics at Northwestern University Feinberg School of Medicine, specializes in atopic dermatitis.

“I’ve been board-certified for over 15 years and have treated thousands of patients with this chronic condition,” said Dr. Lio. “I’ve seen how JAKs can have a positive impact for certain patients who are suffering from moderate-to-severe disease and searching for relief. These treatment options can be a real difference-maker for them.”

Peter Lio, MD, is a Chicago-based dermatologist who has been board-certified for more than 15 years and specializes in atopic dermatitis. Credit: Peter Lio

Understanding JAKs

It is believed that JAKs address an underlying cause of AD by inhibiting the activity of one or more of the Janus kinase family of enzymes, which are involved in overactive immune signaling.⁴ This reduced activity inside the cell may help mitigate AD symptoms, such as skin inflammation and itchiness.^5,6

It is important for dermatologists to have honest, open dialogue with their patients about their symptoms and treatment goals to find the most appropriate treatment approach. “Many JAKs are once-daily oral medications, which some patients may find convenient for their lifestyle as they are easy to take and transport,” added Dr. Lio.

One such medication is Pfizer’s CIBINQO® (abrocitinib), a once-daily prescription pill approved to treat refractory, moderate-to-severe AD in adults and adolescents 12 and up, who haven’t adequately responded to previous systemic treatments or for whom those treatments are inadvisable.⁷

CIBINQO has a BOXED WARNING for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.⁷ Learn more about the risks in the Important Safety Information at the end of this article.

The Science Behind CIBINQO

CIBINQO works by reversibly inhibiting JAK1, which blocks the adenosine triphosphate binding site, disrupting a process that contributes to inflammation.⁷ Dr. Lio says he began prescribing CIBINQO to appropriate patients after reviewing clinical trial results, like the Phase 3 JADE COMPARE study.

This randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of CIBINQO in combination with topical corticosteroids in 838 patients with moderate-to-severe AD for up to 16 weeks.⁶

In the study, patients received one of four treatment options: CIBINQO 100 mg, CIBINQO 200 mg, a biologic treatment, or placebo treatment. The co-primary endpoints of the study were the Investigator’s Global Assessment (IGA) response and the Eczema Area and Severity Index-75 (EASI-75) response at week 12.⁶

Based on the results of the JADE COMPARE trial, at week 12, treatment with CIBINQO considerably reduced skin lesions and itch compared to treatment with a placebo. The IGA response rates were 36% for CIBINQO 100 mg and 47% for CIBINQO 200 mg compared to 14% for placebo. Additionally, the EASI-75 response rates were 58% for CIBINQO 100 mg and 68% for CIBINQO 200 mg, compared to 27% for placebo.⁷

The results also showed that rapid itch relief, a key secondary endpoint, could be achieved with CIBINQO.⁶ The proportion of patients achieving PP-NRS4 (defined as an improvement of ≥4 points from baseline in Peak Pruritus Numerical Rating Scale) at week two was higher in those treated with CIBINQO 200 mg once daily (30%) and 100 mg once daily (14%) in combination with background medicated topical therapies compared to placebo (8%).⁷

The recommended dose is CIBINQO 100 mg. If an adequate response is not achieved with CIBINQO 100 mg after 12 weeks, consider increasing dosage to 200 mg. Discontinue therapy if inadequate response is seen after dosage increase to 200 mg.

“In my practice, I’ve seen many patients who did not respond adequately to biologics. For these patients, I would consider trying them on a JAK next,” said Dr. Lio. “One benefit of JAKs is that they can be fast-acting, with some patients seeing itch improvement in only a few weeks.”

Risks and Considerations

There are potentially serious side effects to consider when prescribing CIBINQO, including:

• Increased risk of serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death, including tuberculosis. Avoid use in patients with active serious infection.
• Higher rate of all-cause mortality including sudden cardiovascular death, with another JAK inhibitor vs tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis (RA). CIBINQO is not approved for use in patients with RA.
• Malignancies, major adverse cardiovascular events and thrombosis have occurred in patients treated with CIBINQO. Avoid use in patients who may be at increased risk of thrombosis.⁷

Screening and regular monitoring are necessary when prescribing CIBINQO. Consider the benefits and risks for the individual patient before initiating or continuing therapy.

Across the CIBINQO clinical trial program, the most commonly reported adverse events (in ≥1% of patients treated with CIBINQO for up to 16 weeks and occurring at a higher rate than with placebo) included nasopharyngitis, nausea, and headache.⁷

Please refer to the Important Safety Information below.

When prescribing any medication, including CIBINQO, dermatologists should discuss the potential benefits and risks with their patients. Explaining this information in a way they can easily understand helps ensure patients are fully informed and fosters more open and collaborative communication.

“Listening is such a critical step,” said Dr. Lio. “Many patients feel unheard, so I make it a priority to listen intently for as long as they need. I want them to know that I am hearing them. Then, I like to outline some options and do shared decision-making together to develop an action plan they feel comfortable with.”

Open, honest communication between doctors and their patients is critical to finding the right treatment approach for each patient. Credit: Getty Images

Finding a Path to Symptom Relief

As trusted resources, dermatologists play a pivotal role in ensuring patients can meet their treatment goals. By openly communicating with patients about their AD symptoms, engaging in shared decision-making, and discussing potential benefits and risks of treatment options like JAK-inhibiting therapies, dermatologists can help improve patient outcomes.

Dr. Lio believes doctors should consider themselves guides to their patients through their therapeutic journey to find the right individualized path. While JAKs may not be for everyone, he believes they may be the right fit for some patients with uncontrolled AD.

“The treat-to-target goal has been elevated in AD,” Dr. Lio explained. “We now have more tools to help people find relief, so we shouldn’t settle for less.”

To learn more about CIBINQO, visit https://cibinqo.pfizerpro.com/.

IMPORTANT SAFETY INFORMATION⁷

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS

SERIOUS INFECTIONS
Patients treated with CIBINQO may be at increased risk for developing serious infections that may lead to hospitalization or death. The most frequent serious infections reported with CIBINQO were herpes simplex, herpes zoster, and pneumonia.

If a serious or opportunistic infection develops, discontinue CIBINQO and control the infection.

Reported infections from Janus kinase (JAK) inhibitors used to treat inflammatory conditions:

• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative latent TB test.
• Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
• Bacterial, viral (including herpes zoster), and other infections due to opportunistic pathogens.

Avoid use of CIBINQO in patients with an active, serious infection, including localized infections. The risks and benefits of treatment with CIBINQO should be carefully considered prior to initiating therapy in patients with chronic or recurrent infections or those who have resided or traveled in areas of endemic tuberculosis or endemic mycoses.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIBINQO, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Consider yearly screening for patients in highly endemic areas for TB. CIBINQO is not recommended for use in patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, or for patients with a negative test for latent TB but who are at high risk for TB infection, start preventive therapy for latent TB prior to initiation of CIBINQO.

Viral reactivation, including herpes virus reactivation (eg, herpes zoster, herpes simplex), was reported in clinical studies with CIBINQO. If a patient develops herpes zoster, consider interrupting CIBINQO until the episode resolves. Hepatitis B virus reactivation has been reported in patients receiving JAK inhibitors. Perform viral hepatitis screening in accordance with clinical guidelines before starting therapy and monitor for reactivation during therapy with CIBINQO. CIBINQO is not recommended for use in patients with active hepatitis B or hepatitis C.

MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another JAK inhibitor to TNF blocker treatment, a higher rate of all-cause mortality (including sudden cardiovascular death) was observed with the JAK inhibitor. CIBINQO is not approved for use in RA patients.

MALIGNANCIES
Malignancies, including non-melanoma skin cancer (NMSC), were reported in patients treated with CIBINQO. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. Perform periodic skin examination for patients who are at increased risk for skin cancer. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA patients. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
Major adverse cardiovascular events were reported in patients treated with CIBINQO. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. CIBINQO is not approved for use in RA patients. Patients who are current or past smokers are at additional increased risk. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

THROMBOSIS
Deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients treated with CIBINQO. Thrombosis, including PE, DVT, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of overall thrombosis, DVT, and PE were observed when compared with TNF blockers. CIBINQO is not approved for use in RA patients.

Avoid CIBINQO in patients that may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue CIBINQO and treat patients appropriately.

CONTRAINDICATION
CIBINQO is contraindicated in patients taking antiplatelet therapies, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment.

LABORATORY ABNORMALITIES
Hematologic Abnormalities: Treatment with CIBINQO was associated with an increased incidence of thrombocytopenia and lymphopenia. Prior to CIBINQO initiation, perform a complete blood count (CBC). CBC evaluations are recommended at 4 weeks after initiation and 4 weeks after dose increase of CIBINQO. Discontinuation of CIBINQO therapy is required for certain laboratory abnormalities.

Lipid Elevations: Dose-dependent increase in blood lipid parameters were reported in patients treated with CIBINQO. Lipid parameters should be assessed approximately 4 weeks following initiation of CIBINQO therapy, and thereafter patients should be managed according to clinical guidelines for hyperlipidemia. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

IMMUNIZATIONS
Prior to initiating CIBINQO, complete all age-appropriate vaccinations as recommended by current immunization guidelines, including prophylactic herpes zoster vaccinations. Avoid vaccination with live vaccines immediately prior to, during, and immediately after CIBINQO therapy.

RENAL IMPAIRMENT
Avoid use in patients with severe renal impairment or end stage renal disease, including those on renal replacement therapy.

HEPATIC IMPAIRMENT
Avoid use in patients with severe hepatic impairment.

ADVERSE REACTIONS
Most common adverse reactions (≥1% with CIBINQO 100 mg) are nasopharyngitis, nausea, headache, herpes simplex, increased blood creatine phosphokinase, dizziness, urinary tract infection, fatigue, acne, vomiting, impetigo, oropharyngeal pain, hypertension, influenza, gastroenteritis, and dermatitis contact.

Most common adverse reactions (≥1% with CIBINQO 200 mg and greater than CIBINQO 100 mg) are nausea, headache, herpes simplex, increased blood creatine kinase, dizziness, urinary tract infection, acne, vomiting, gastroenteritis, upper abdominal pain, abdominal discomfort, herpes zoster, and thrombocytopenia.

Inform patients that retinal detachment has been reported in CIBINQO clinical trials. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision.

DRUG INTERACTIONS
Monitor appropriately or dose titrate P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities when coadministered with CIBINQO. See Prescribing Information for clinically relevant drug interactions.

USE IN PREGNANCY
Available data from pregnancies reported in clinical trials with CIBINQO are not sufficient to establish a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise patients who can become pregnant that CIBINQO may impair fertility.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CIBINQO during pregnancy. Pregnant women exposed to CIBINQO and health care providers are encouraged to call 1-877-311-3770 or visit CIBINQOPregnancyRegistry.com.

LACTATION
Advise patients not to breastfeed during treatment with CIBINQO and for one day after the last dose.

Please see full Prescribing Information, including BOXED WARNING, and Medication Guide.

What is CIBINQO?⁷

CIBINQO is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Limitations of Use: CIBINQO is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

References:

1. Frazier W, Bhardwaj N. Atopic dermatitis: diagnosis and treatment. Am Fam Physician. 2020;101(10):590-598.
2. AAAAI/ACAAI JTF Atopic Dermatitis Guideline Panel; Chu DK, Schneider L, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations. Ann Allergy Asthma Immunol. 2024;132(3):274-312.
3. Mikhaylov D, Ungar B, Renert-Yuval Y, Guttman-Yassky E. Oral Janus kinase inhibitors for atopic dermatitis. Ann Allergy Asthma Immunol. 2023;130(5):577-592.
4. Lin CM, Cooles FA, Isaacs JD. Basic mechanisms of JAK inhibition. Mediterr J Rheumatol. 2020 Jun 11;31(Suppl 1):100-104.
5. He Q, Xie X, Chen Q, et al. Janus kinase inhibitors in atopic dermatitis: an umbrella review of meta-analyses. Front Immunol. 2024;23;15:1342810.
6. Bieber T, Simpson EL, Silverberg JI, et al; for the JADE COMPARE Investigators. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101-1112
7. CIBINQO Package insert. Pfizer Inc; 2023
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