We thank Marzano et al for their interest in our article1 and agree that understanding the background risk of venous thrombotic events (VTEs) in chronic inflammatory skin diseases (CISDs) is critical. The CISDs selected for this initial study were among the more common and currently have multiple clinical trials assessing Janus kinase (JAK) inhibitors, a target potentially associated with VTE risk, for these indications. Future studies are under way to investigate VTE risk in very rare CISDs that affect different patient populations, such as bullous pemphigoid. We agree there is differential risk between dermatologic conditions, and it is critical not to extrapolate the results from 1 set of patients to another.
In the recent ORAL Surveillance (NCT02092467) randomized phase 3b/4 clinical trial in patients with rheumatoid arthritis, investigators saw an increased risk of VTE among those patients treated with a JAK inhibitor (tofacitinib) of 3.3 to 7/1000 person-years vs tumor necrosis factor inhibitors (2.2/1000 person-years).2 The incidence of VTE in patients with CISDs in our article1 was 0.6 to 1.5/1000 person-years, and as expected lower than the background incidence in patients with rheumatoid arthritis with or without JAK inhibitor use. Future studies will build on this foundation to determine if VTE risk with JAK inhibition is similarly raised among patients with skin disorders, or whether the lower baseline risk is protective.
By establishing a baseline risk, our findings can be used to contextualize VTE risk signals emerging from randomized clinical trials of systemic immunomodulatory agents like JAK inhibitors and spontaneous adverse event reports from current off-label use. Although the focus of our study was on interdisease differences, as JAK inhibitors and other emerging medications are applied to dermatology patients with substantial comorbidities, research needs to be expanded to identify intradisease variations of VTE as a function of patient characteristics. Over time, this will allow for improved patient selection and informed shared decision-making as the advantages of highly effective novel therapeutics is balanced with the challenge of new potential risks.
Footnotes
Conflict of Interest Disclosures: Dr Mostaghimi reported personal fees from hims and hers, Digital Diagnostics, Pfizer, Concert, Lilly, and AbbVie outside the submitted work as well as service as an Associate Editor of JAMA Dermatology. Dr Silverberg is an advisor/speaker/consultant for AbbVie, Afyx, Arena, Asana, BioMX, Bluefin, Bodewell, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo, Luna, Menlo, Novartis, Pfizer, RAPT, Regeneron, and Sanofi; a speaker for Eli Lilly, Pfizer, Regeneron, and Sanofi; and his institution received grants from Galderma. No other disclosures were reported.
Contributor Information
Maria C. Schneeweiss, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Letters Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts.
Jonathan I. Silverberg, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC.
Arash Mostaghimi, Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts; Associate Editor, JAMA Dermatology.
References
- 1.Schneeweiss MC, Kim SC, Wyss R, et al. Incidence of venous thromboembolism in patients with dermatologist-diagnosed chronic inflammatory skin diseases. JAMA Dermatol. 2021;157(7):805–816. doi: 10.1001/jamadermatol.2021.1570 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Charles-Schoeman C, Fleischmann R, Mysler E, et al. The risk of venous thromboembolic events in patients with RA aged ≥ 50 years with ≥ 1 cardiovascular risk factor: results from a phase 3b/4 randomized safety study of tofacitinib vs TNF inhibitors. Accessed September 21, 2021. https://acrabstracts.org/abstract/the-risk-of-venous-thromboembolic-events-in-patients-with-raaged-%e2%89%a5-50-years-with-%e2%89%a5-1-cardiovascular-risk-factor-results-from-a-phase-3b-4-randomized-safety-study-of-tofacitinib-vs-tn/