Chronic Pruritus: A Review of Neurophysiology and Associated Immune Neuromodulatory Treatments

Jay M. Patel, BSc; Harry Dao Jr., MD, FAAD


Skin Therapy Letter. 2018;23(5):5-9. 

In This Article

Immune-modulatory Agents in Chronic Pruritus Associated Disorders

Using their basic science findings as rationale, Oetjen et al. set-up an experimental trial to explore if JAK signaling might be a novel therapeutic target in chronic idiopathic pruritus (CIP) patients with no overt signs of inflammation. In this short investigation, the researchers treated five CIP patients with oral tofacitinib, a JAK inhibitor, and found a significant reduction in their itching as quantified by a 0–10 numerical rating scale.[3] This finding is summarized in Table 1.

Other recent clinical trials have also focused on specific immune modulators to treat moderate-to-severe AD in patients who have failed conventional topical treatments to alleviate their itch symptoms. These have included blockade of IL-4Ra receptor, JAK, or IL-31Ra receptor signaling.[13–17,20] Select clinical and experimental trials utilizing these drugs are presented in Table 1. Overall, there appears to be positive treatment responses to these treatments with minimal side effects. Dupilumab, an IL-4Ra receptor antagonist, has been the most studied, with large-scale clinical trials showing dose dependent improvements in symptoms. Based on the phase 2 trials, weekly subcutaneous 300 mg with topical glucocorticoids appears to elicit the best response, however, the measured outcomes used between trials are different and subject numbers vary greatly. Dupilumab was recently approved by the US Food and Drug Administration on March 28, 2017 for moderate-to-severe eczema (AD) at an initial dose of 600 mg (two 300 mg injections) followed by 300 mg injections every other week.[21] Tofacitinib has also been assessed in clinical and experimental trials in both ointment and oral forms, and demonstrated signs of improvement in both AD and CIP. Although the oral tofacitinib trials are very small and neither placebo controlled nor blinded, they did show improvement of symptoms in both AD and CIP patients as measured by body surface involvement and itch cessation, respectively. Lastly, a recent trial published on nemolizumab, an IL-31Ra antagonist, reported a dose-dependent response in pruritus reduction.