Reply to "Does hydroxychloroquine work for chronic spontaneous urticaria?"

Abstract

We appreciate Kaplan’s comments regarding our recently published retrospective study examining relative clinical effectiveness of hydroxychloroquine (HCQ) versus omalizumab in patients with chronic spontaneous urticaria (CSU) unresponsive to antihistamines.1Kaplan A.P. Does hydroxychloroquine work for chronic spontaneous urticaria?.J Allergy Clin Immunol Pract. 2023; 11: 1983Abstract Full Text Full Text PDF Google Scholar,2Khan N. Epstein T.G. DuBuske I. Strobel M. Bernstein D.I. Effectiveness of hydroxychloroquine and omalizumab in chronic spontaneous urticaria: a real-world study.J Allergy Clin Immunol Pract. 2022; 10: 3300-3305Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar He identifies a modest complete response rate to HCQ of 35% in our study after 3 months of treatment, like placebo responses in published double-blind placebo-controlled trials of omalizumab. We agree that the effect size at 3 months is modest, but we found a compelling 66% complete response rate after 1 year of HCQ treatment. This 1-year complete response rate with HCQ far exceeds any possible improvement attributable to the small number of patients who might have experienced spontaneous resolution of CSU. We concur with Kaplan’s experience that clinical responses are unlikely within the first 1 month of HCQ treatment, and as we clearly emphasized, a trial of 3 to 12 months is necessary to assess the effectiveness of HCQ in antihistamine-refractory CSU patients. As we stated, the delay in onset of action for CSU is consistent with what has been observed with HCQ in treating autoimmune disorders.3Carmichael S.J. Charles B. Tett S.E. Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis.Ther Drug Monit. 2003; 25: 671-681Crossref PubMed Scopus (0) Google Scholar Our study was unique because it described treatment outcomes in a large, well-defined CSU patient population that had failed standard therapy before starting HCQ (n = 111) or omalizumab (n = 134). We acknowledge in the discussion that the retrospective nature of the study is a limitation, and a prospective placebo-controlled trial should be conducted in the future. This would be possible in an ideal world in which extramural funding is readily available for conducting well-powered controlled clinical trials to justify repurposing old drugs such as HCQ for a new CSU indication. For this reason, it is unlikely that large double-blind placebo controlled studies of HCQ or other anti-inflammatory drugs (eg, methotrexate or sulfasalazine) will ever be conducted. Cyclosporin is one exception for which placebo-controlled studies have shown efficacy for CSU.4Zuberbier T. Abdul Latiff A.H. Abuzakouk M. Aquilina S. Asero R. Baker D. et al.The international EAACI/GA(2)LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.Allergy. 2022; 77: 734-766Crossref PubMed Scopus (197) Google Scholar However, more than 60% of patients experience adverse effects to cyclosporin, and close laboratory monitoring for renal toxicity is required, which limits its use.5Kessel A. Toubi E. Cyclosporine-A in severe chronic urticaria: the option for long-term therapy.Allergy. 2010; 65: 1478-1482Crossref PubMed Scopus (87) Google Scholar,6Savic S. Marsland A. McKay D. Ardern-Jones M.R. Leslie T. Somenzi O. et al.Retrospective case note review of chronic spontaneous urticaria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK secondary care.Allergy Asthma Clin Immunol. 2015; 11: 21Crossref PubMed Scopus (36) Google Scholar There is clearly an unmet need for alternative therapeutic agents to address refractory CSU patients who are unresponsive to omalizumab and for patients who are unable to afford long-term treatment with biologic agents. We are hopeful that future treatment parameters or guideline committees will consider HCQ in future CSU treatment algorithms, even in the absence of DBPC studies. The authors applaud The Journal of Allergy and Clinical Immunology: In Practice for publishing these retrospective real-world data showing the clinical effectiveness and safety of HCQ in CSU. Ultimately, clinicians and patients are the final arbiters in selecting safe and effective management options, including some not yet incorporated in practice guidelines. Does hydroxychloroquine work for chronic spontaneous urticaria?The Journal of Allergy and Clinical Immunology: In PracticeVol. 11Issue 6PreviewThe December 2022 issue of The Journal of Allergy and Clinical Immunology: In Practice contains a real-world study of the effectiveness of hydroxychloroquine versus omalizumab as add-on therapy for patients with antihistamine-resistant chronic spontaneous urticaria (CSU).1 This is based on a retrospective chart review of 265 patients in two centers over a 5-year interval. A complete response to omalizumab of 82% is noted at 3 months compared with 35% for hydroxychloroquine. The authors acknowledge that there is no placebo control, but if we assume a placebo effect of 25% to 30%, as documented in three prior double-blind controlled studies of omalizumab that included over 900 patients, it leaves an 8% to 13% success rate for hydroxychloroquine at 3 months. Full-Text PDF