Treating Chronic Itch: Therapeutic Review

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Itch is “learned” in the nervous system, said Dr Berger, with involvement by both central and peripheral neural processes.
Itch is “learned” in the nervous system, said Dr Berger, with involvement by both central and peripheral neural processes.

The following article is part of conference coverage from the 2018 Fall Clinical Dermatology Conference in Las Vegas, Nevada.Dermatology Advisor's staff will be reporting breaking news associated with research conducted by leading experts in dermatology. Check back for the latest news from Fall Clinical Derm 2018.

During a plenary session at the 2018 Fall Clinical Dermatology Conference in Las Vegas, Nevada, Brian Berman, MD, PhD, professor emeritus of dermatology and cutaneous surgery at the University of Miami Miller School of Medicine, and co-director of the Center for Clinical and Cosmetic Research Skin and Cancer Associates, discussed findings from various studies exploring the effects of agents used to treat pruritis, including those highlighted below.

Interleukin-31 (IL-31) is a pruritogenic cytokine involved in the itch-scratch cycle that exacerbates atopic dermatitis (AD). Nemolizumab (CIM331), a humanized antibody against IL-31 receptor A, is proposed to “improve pruritis and ameliorate dermatitis by breaking [the] itch-scratch cycle,” according to Dr Berman. In a recent phase 2 randomized, double-blind, placebo-controlled trial lasting 12 weeks, 264 patients with poorly controlled, moderate to severe AD received subcutaneous nemolizumab at varying doses or placebo every 4 weeks.1

The results showed significant improvements on the pruritis visual-analogue scale at each dose studied: 0.1 mg (-43.7%), 0.5-mg (-59.8%), and 2.0 mg (-63.1%) per kg of body weight, compared with -26.6% for placebo (P <.01). Rates of discontinuation were similar between all groups. The nemolizumab group experienced AD exacerbation and peripheral edema more frequently than the placebo group. A previous trial found reductions in pruritus, sleep disturbance, and topical use of hydrocortisone in patients who received a single dose of CIM331.2

Tapinarof is a topical nonsteroidal anti-inflammatory agent that activates the aryl hydrocarbon receptor (AhR). In a double-blind randomized 6-arm trial (1:1:1:1:1:1) published in 2017, treatment of moderate to severe AD with tapinarof cream at 2 concentrations and application frequencies was associated with 12-week success rates of 53% (1% BID); 46% (1% QD); 37% (0.5% BID); 34% (0.5% QD); 24% (vehicle BID); and 28% (vehicle QD) in adolescents and adults.3 A greater number of adverse events of mild to moderate intensity occurred with tapinarof (56%) vs vehicle (41%).

Hypochlorous acid (HOCl) is “naturally generated during immune responses in activated neutrophils by myeloperoxidase-mediated peroxidation of chloride ions,” Dr Berman stated. In a 2013 investigator-blinded randomized Phase 2 study, 73.7% of patients with AD who were treated with an HOC1-containing solution (n=19) showed a reduction in itching over the 3-day study period, compared with 30.0% of those in a group that received no treatment (n=10).4 No serious adverse effects or treatment-related discontinuations were observed. HOCl may reduce pruritus in AD via microbicidal qualities and “anti-inflammatory qualities that reduce the activities of histamine, leukotriene B4, and interleukin-2, all of which contribute to the pathophysiology of itch,” wrote the authors of the study.

The efficacy and safety of omalizumab, an anti-IgE monoclonal antibody, was investigated in a 2013 phase 3, randomized, double-blind trial that included 323 patients with moderate to severe chronic idiopathic urticaria who had not adequately responded to H-antihistamine therapy.5 At the 12-week mark, the mean (±SD) change in a weekly itch-severity score was as follows for each group: -5.9±6.5 in the 75-mg group (P =.46), -8.1±6.4 in the 150-mg group (P =.001), -9.8±6.0 in the 300-mg group (P <.001), and 5.1±5.6 in the placebo group. A similar frequency of adverse effects was noted across all groups.

Dr Berman also mentioned the link between itch and cancer. A 2018 cross-sectional study demonstrated greater odds of malignancy among patients with vs without pruritis (odds ratio 5.76), particularly in those with cancers of the hematopoietic system, skin, and liver.6

In addition, Timothy G. Berger, MD, a dermatologist at the University of California, San Francisco Medical Center, discussed the role of the nervous system in pruritis, stating that itch is “learned” in the nervous system, with involvement by both central and peripheral neural processes. Neural topical therapies for itch were reviewed, including methol/camphor, pramoxine, capsaicin, botox, and more.

Dr Berger cited gabapentin as the initial therapy for pruritis, with 1 of the following added as needed: doxepin, marinol, mirtazapine or paroxetine, naltrexone, or mexiletine. Emerging neural therapies for pruritis include topical TrkA inhibitors, NK-1 inhibitors, kappa opioid agonists, and GABA receptor antagonists.  

For more coverage of Fall Clinical Derm 2018, click here.

References

  1. Ruzicka T, Hanifin JM, Furue M, et al; XCIMA Study Group. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017; 376(9):826-835.
  2. Nemoto O, Furue M, Nakagawa H, et al. The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2016; 174(2):296-304.
  3. Smith SH, Jayawickreme C, Rickard DJ, et al. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol. 2017; 137(10):2110-2119.
  4. Berman B, Nestor M. An investigator blinded randomized study evaluating hypochlorous acid (HOCl) in the treatment of atopic dermatitis-associated pruritis. https://mauiderm.com/an-investigator-blinded-randomized-study-evaluating-hypochlorous-acid-hocl-in-the-treatment-of-atopic-dermatitis-associated-pruritus/. Accessed October 18, 2018.
  5. Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013; 368(10):924-35.
  6. Larson VA, Tang O, Stander S, Kang S, Kwatra SG. Association between itch and cancer in 16,925 pruritus patients: Experience at a tertiary care center. J Am Acad Dermatol. 2018. doi:10.1016/j.jaad.2018
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