Comparing available JAK inhibitors for treating patients with psoriasis

ABSTRACT

Introduction

Cytokine blockers have revolutionized the management of psoriasis. While efficacious, not all patients respond, and treatment may lose efficacy over time. Janus kinase (JAK) inhibitors target the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) transduction cascade from transmitting cytokine signals in psoriasis.

Areas covered

A PubMed search of phase I, II, and III clinical trials published between 2012 and 2021 utilizing the key terms: Janus kinase and psoriasis. Our search was expanded from clinical trials to further investigate the pathophysiology, standard of care, and safety and efficacy of JAK inhibitors in psoriasis.

Expert opinion

Current treatments for psoriasis include topicals, phototherapy, and systemic therapy. The subcutaneous or intravenous route of biologic administration presents a challenge as patients often prefer oral medications over injections and because of anti-drug antibody development. Tofacitinib is effective and has an overall mild-to-moderate safety profile but includes an FDA black box warning for increased risk of cardiovascular events and malignancy. Other JAK inhibitors have an acceptable safety profile and are effective in early clinical trials. Poor topical medication adherence should be considered when evaluating JAK inhibitors. Oral JAK inhibitors may provide a preferable route of administration and improved clinical outcomes.

KEYWORDS:

• Janus kinase
• psoriasis
• psoriatic arthritis
• tofacitinib
• safety
• efficacy
• dermatology
• psoriasis area and severity index

Article highlights

• The pathophysiology of psoriasis involves localized immune cells that produce cytokines Interleukin (IL) −23 and Tumor Necrosis Factor alpha (TNF-α), which induce differentiation of T-helper (T_H) −17 cells through the JAK/STAT pathway and leads to IL-17 mediated hyperkeratosis and inflammation.

• JAK inhibitors are an emerging treatment option for psoriasis that selectively inhibit different enzymes in the JAK/STAT pathway.

• Oral tofacitinib is a JAK1/JAK3 inhibitor that is well characterized through phase III clinical trials but is not yet FDA approved for use in plaque psoriasis.

• Eight other JAK inhibitors are undergoing clinical trials for use in plaque psoriasis.

• Oral tofacitinib and upadacitinib are FDA approved for use in psoriatic arthritis, and several other JAK inhibitors are undergoing clinical trials for use in psoriatic arthritis.

• Topical JAK inhibitors are undergoing clinical trials; however, medication adherence must be followed for increased efficacy.

• The reported adverse effects for oral JAK inhibitors are increased incidence of herpes zoster (HZ) infections, increased lipids and liver enzymes, and decreased neutrophils and hemoglobin. In a long-term open-label study of oral tofacitinib, prostate (n=15), lung (n=9), and breast cancer (n=6) and, although rare, major adverse cardiac events (MACE) were reported. The FDA issued a black box warning for increased risk of serious infection, mortality, malignancy, MACE, and thrombosis for all approved JAK inhibitors.

• Selective JAK inhibitors may provide similar efficacy with a better safety profile in comparison to non-selective JAK inhibitors.

Additional information

Funding

This paper was not funded.