The late-stage atopic dermatitis(AD) pipeline is full of promising candidates, including the Janus kinase (JAK) inhibitor class. JAK inhibitors provide a more convenient option for patients who prefer topical or oral agents for treatment, however there are some class-wide safety concerns, such as increased risk of major cardiovascular events and malignancies, which may limit their use. Key JAK inhibitors in development for or recently approved for AD include four oral agents, Lilly/Incyte’s Olumiant (baricitinib), AbbVie’s Rinvoq (upadacitinib), Pfizer’s Cibinqo (abrocitinib), and Asana Bioscience’s gusacitinib, as well as two topical agents, Incyte’s Opzelura (ruxolitinib) and LEO pharma’s Corectim (delgocitinib). Olumiant, Rinvoq and Cibinqo have all been approved in the 4EU + UK and Japan, while Opzelura and Corectim have been approved in the US and Japan, respectively.

Although the majority of JAK inhibitors in late-stage development for AD are targeting moderate-to-severe patients, Opzelura is being positioned for patients with mild-to-moderate disease. The potential availability of a new mechanism of action for patients with a milder disease could have a strong impact on market dynamics.

As part of GlobalData’s upcoming report on the AD market, “GlobalData: Atopic Dermatitis: Global Drug Forecast and Market Analysis to 2030,” GlobalData conducted a survey of high-prescribing physicians (primary care physicians, paediatricians, and dermatologists) from the seven major markets (7MM: US, 4EU [France, Germany, Italy, and Spain], the UK, and Japan). Physicians were asked their opinions on the upcoming launches of oral and topical JAK inhibitors and how likely, on a scale of 1-5, with five being most likely and one being least likely, they would be to prescribe them to their patients. Physicians were also given the option to provide a short, written explanation for their score.

Figure one depicts, on average, how likely physicians across the 7MM were to prescribe JAK inhibitors, comparing oral and topical. While physicians were unsure on oral JAK inhibitor use, they were generally more optimistic about the introduction of topical JAK inhibitors.

The survey data showed that physicians across the 7MM were only modestly enthusiastic about the introduction of oral JAK inhibitors, as exemplified by the mediocre scores of 3.0-3.3 out of 5. The biggest division was seen in the 4EU + UK where doctors noted that, even though they are highly effective, they can only be used in a specific group of patients, such as those with inadequate responses or adverse effects to biologics. However, some 4EU + UK physicians mentioned that there is a real need for therapies in the treatment refractory group because not all patients respond well to Sanofi and Regeneron’s IL-4/13 inhibiting biologic Dupixent (dupilumab).

In the US, physicians stressed the need for more studies to further analyse the risk-benefit profile of JAK inhibitors, as well as expressed concerns around the boxed warning. Similarly, Japanese physicians were cognisant of JAK inhibitors’ strong efficacy profile but mentioned that cost and safety are two key factors preventing them from potentially prescribing with confidence. While it is clear that oral JAK inhibitors are extremely efficacious, it is ultimately their safety profile that is holding them back, but the narrative is slightly different for the topical JAK inhibitors.

GlobalData’s survey data highlighted that, while physicians in the US and Japan were more optimistic about the introduction of topical JAK inhibitors over oral JAK inhibitors, in the 4EU + UK, physicians were equally unenthused about the two modes of administration. US physicians commented that non-steroidal options are always welcomed and that if approved, topical JAK inhibitors would give patients more choice. Japanese doctors echoed the latter, but also stressed that safety issues cannot be ignored. EU physicians highlighted the importance of patient preferences and stressed that the price will likely limit the use of topical JAK inhibitors. UK physicians were somewhat sceptical but stated that they would be more convinced once topical JAK inhibitors were approved, although safety monitoring would be necessary.

Overall, GlobalData’s 2021 survey results suggest that the integration of JAK inhibitors into the AD treatment paradigm may differ by route of administration. Based on GlobalData’s primary research, it is clear that safety is a key reason for the wavering confidence in the class, but with the correct patient selection and monitoring, JAK inhibitors have the ability to transform the space.