Janus Kinase Inhibitors in the Treatment of Atopic Dermatitis: Military Considerations
Janus kinase (JAK) inhibitors represent one of the newest and most promising additions to the available treatments of atopic dermatitis (AD). Janus kinase inhibitors offer several key benefits over injectable biologics to include more predictable pharmacokinetics, nonimmunogenicity, and flexible dosing, in addition to their oral and topical bioavailability. Recommended laboratory assessments before and during treatment in addition to medication side effects may limit the scope of use in the active-duty military population and specifically within special-duty populations. In this article, we review approved and emerging JAK inhibitors for the treatment of AD as well as important considerations for both military and nonmilitary patient populations.
Practice Points
- Oral Janus kinase (JAK) inhibitors are novel therapies available for the treatment of atopic dermatitis (AD), with multiple recently approved agents within the class.
- Recommended laboratory monitoring during treatment with oral JAK inhibitors may limit the use of these medications in the active-duty military population or in those with special-duty assignments.
- The oral and topical bioavailability of these medications makes them a more feasible option for deploying service members or for those requiring flexible dosing.
- The rapid improvement in AD seen in multiple trials of oral JAK inhibitors suggests these agents could prove useful in management of acute AD flares, especially in military environments, where injectable agents are either unavailable or unsupported.
Use of oral JAK inhibitors in active-duty service members is less ideal for multiple reasons. A large randomized safety clinical trial of patients with rheumatoid arthritis who received tofacitinib and methotrexate was required by the FDA to evaluate the risk of MACEs, malignancy, and infections associated with JAK inhibitor treatment. Data from this trial showed a dose-dependent increased risk for MACEs, all-cause mortality, and thrombosis at both doses of tofacitinib compared with tumor necrosis factor inhibitors and a non–dose-dependent increased risk for malignancy excluding nonmelanoma skin cancer.28 In contrast to the MACE and VTE data from patients with diseases other than AD treated with JAK inhibitors, there has been only 1 patient who developed a pulmonary embolism while being treated with baricitinib 4 mg.22,29 Downstream effects from the above study were label recommendations to reserve the medicines for patients who had an inadequate response or intolerance to 1 or more tumor necrosis factor blockers and to carefully consider risks vs benefits in patients, in particular current or prior smokers, those with other cardiovascular risk factors or a history of VTE, and those with a malignancy history other than already treated nonmelanoma skin cancer.28
There are consistent observations of laboratory abnormalities with JAK inhibitors, as discussed above, to include creatine phosphokinase elevation and cytopenias.30 Although existing data demonstrate that cytopenias are less of a concern in the AD population compared with the rheumatoid arthritis population, baseline and periodic laboratory monitoring are still recommended. In general, pretreatment laboratory assessment prior to initiating an oral JAK inhibitor should consist of a complete blood cell count with differential, complete metabolic panel, tuberculosis screening, chronic hepatitis panel, HIV screening, and a fasting lipid panel.2 The feasibility of obtaining these laboratory measurements in an operational setting or sea-going platform is limited, but many deployed locations and naval vessels possess the laboratory capability to perform a complete blood cell count and complete metabolic panel. Overall tolerability of oral JAK inhibitors in the treatment of AD appears favorable based on studies that were mostly 16 weeks in duration. Few recent longer-term studies have confirmed this side effect profile, but additional studies are needed.
Final Thoughts
Janus kinase inhibitors are a promising therapeutic class with multiple recently FDA-approved agents for the treatment of moderate to severe AD, with new agents on the horizon. Available efficacy data are promising and balanced by a favorable safety profile in clinical trials to date. The oral and topical bioavailability of JAK inhibitors makes them attractive alternatives to existing therapies. The rapidity of itch reduction and AD improvement demonstrated in multiple trials has the potential to decrease the length of limited-duty assignments, potentially returning treated service members to full-duty status more expeditiously. Other applications include use of these medications in scenarios where injectable medications are either unavailable or unsupported.
In the active-duty population, both the condition and/or the treatment may be duty limiting. Service members with AD who require more than topical treatment may require a medical evaluation board to determine if they are still fit to serve. The deployed environment routinely exacerbates AD and exposes service members to infections and environments where immunosuppression can create more risks than in the general population. Nonbiologic medications, which do not require refrigeration, are an exciting option for our patients with AD, including those actively serving or considering serving in the military. However, all factors in any patient’s life should be considered. Therefore, it is important for the nonmilitary dermatologist to work with local military physicians and the patient to determine the optimal treatment regimen to result in the best possible outcome.
