Use of systemic Janus kinase inhibitors for dermatologic indications in the elderly: A retrospective study of 67 cases
Authors: M Grace Hren, Saakshi Khattri
Journal: Journal of the American Academy of Dermatology (2023)

Systemic Janus kinase inhibitors (JAK-inhs) are a novel treatment option approved for use in several inflammatory conditions that span dermatology, rheumatology, and gastroenterology. Side effects associated with JAK-inhs in the general patient population include infections, increased lipids, cytopenias, major adverse cardiovascular events, thromboembolic events, herpes, and malignancies.1Klein B. Treudler R. Simon J.C. JAK-inhibitors in dermatology – small molecules, big impact? Overview of the mechanism of action, previous study results and potential adverse effects.J Dtsch Dermatol Ges. 2022; 20: 19-24https://doi.org/10.1111/ddg.14668Crossref Scopus (40) Google Scholar Many clinical trials detail the use of JAK-inhs for dermatologic indications; however, elderly patients (aged ≥65 years) are often excluded from these studies. In the few trials that do enroll elderly patients, oftentimes, the data are not stratified in a way that allows for meaningful conclusions to be drawn (eg, data are stratified into age groups of <18 years and ≥18 years only).2Guttman-Yassky E. Teixeira H.D. Simpson E.L. et al.Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials.Lancet. 2021; 397: 2151-2168https://doi.org/10.1016/S0140-6736(21)00588-2Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar In the few studies that include and stratify elderly patients into a separate category, a slight increase was noted in the risk of adverse hematological events and herpes zoster; however, these studies had an extremely small sample size of elderly patients.3Simpson E.L. Sinclair R. Forman S. et al.Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.Lancet. 2020; 396: 255-266https://doi.org/10.1016/S0140-6736(20)30732-7Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar, 4Simpson E.L. Silverberg J.I. Nosbaum A. et al.Integrated safety analysis of abrocitinib for the treatment of moderate-to-severe atopic dermatitis from the phase II and phase III clinical trial program.Am J Clin Dermatol. 2021; 22: 693-707https://doi.org/10.1007/s40257-021-00618-3Crossref PubMed Scopus (56) Google Scholar, 5Cline A. Cardwell L.A. Feldman S.R. Advances in treating psoriasis in the elderly with small molecule inhibitors.Expert Opin Pharmacother. 2017; 18: 1965-1973https://doi.org/10.1080/14656566.2017.1409205Crossref PubMed Scopus (14) Google Scholar As such, there is currently a lack of knowledge regarding real-world use of JAK-inhs in the elderly. We performed a retrospective chart review to assess the use of systemic JAK-inhs in this group at a large academic institution. Any man or woman aged ≥65 years and prescribed a systemic JAK-inh between August 1, 2018, and August 1, 2023, at Mount Sinai and a tertiary clinic was included in this study. Age, primary diagnosis, medical history, JAK-inh used, concurrent systemic medications, disease status, adverse events, follow-up visits, laboratory results, and duration of therapy were recorded. This study was approved by the Mount Sinai Institutional Review Board. There were 67 elderly patients prescribed JAK-inhs during the outlined dates, with an average age of 71.2 years and an average duration of treatment of 320.2 days. Most commonly, upadacitinib 15 mg daily was prescribed (47.1%). Indications for treatment included atopic dermatitis (26.8%), psoriatic arthritis (49.2%), alopecia areata/universalis (14.9%), and other less frequent off-label indications. Several patients were prescribed concomitant systemic medications (35.8%). Several patients had multiple concurrent inflammatory diseases for which 1 JAK-inh was indicated (Table I; Supplementary Table I, available via Mendeley at https://data.mendeley.com/datasets/9s4ytnznkm/1).Table ICharacteristics of 37 elderly patients prescribed Janus kinase inhibitors for dermatologic disease†History of breast cancer (Lobular carcinoma in situ), patient in remission since 2015.JAK inhibitorNo. of patients∗Total of "Reason for treatment" may not equal total of "No. of patients" on each therapy as several patients were prescribed 1 Janus kinase inhibitor for multiple diagnoses.Average age (y)Average daysReason for treatment∗Total of "Reason for treatment" may not equal total of "No. of patients" on each therapy as several patients were prescribed 1 Janus kinase inhibitor for multiple diagnoses.Concomitant systemic therapiesHigh-risk categoryImproved/no change/worsened/unknownNo. of AEsUpadacitinib, 15 mg3071.5230.4AD (16)PSA (14)PG (1)DM (2)GA (1)AA (2)Ixekizumab (2)Brodalumab (1)Apremilast (1)Methotrexate (3)Risankizumab (1)Prednisone (3)Minoxidil (1)LeflunomideFormer smoker (2)HLD (7)DLD (4)HCL (3)Hx NMSC (3)Melanoma (1)LTBI (1)Hepatitis BHx breast cancer (1)†History of breast cancer (Lobular carcinoma in situ), patient in remission since 2015.HTN (9)T2DM (4)CAD (2)Hx of DVT (1)Hx of stroke (2)22/3/1/44Upadacitinib, 30 mg874.9272.9PF (1)AD (4)PSO/PSA (4)Prednisone (2)Acitretin (1)Methotrexate (1)Risankizumab (1)Dupilumab (1)HTN (1)HLD (2)HCL(4)LTBI (1)Hx of prostate cancer (1)CAD (2)IBD (1)T2DM (1)Hx of NMSC (1)Hx of CAS (1)6/1/0/12Abrocitinib, 100 mg266.5289.5AD (2)N/AHLD (1)HCL (1)1/0/0/10Baricitinib, 2 mg571.5241.6LV (1)AA (3)AU (1)Hydroxychloroquine (1)Minoxidil (2)Rifampin, ethambutol, azithromycin (1)Mycobacterium avium complex, bronchiectasis, COPD (1)Hx of fallopian tube carcinoma (1)HTN (1)HLD (1)3/1/1/00Baricitinib, 4 mg468.0184.6AA (4)N/AHistory of NMSC (2)RA (1)HCL (1)3/0/0/10Tofacitinib, 5 mg470.0747.5Morphea (1)AA (1)PSA (2)Apremilast (1)Sulfasalazine (1)HLD (1)HTN (1)CAD (1)3/0/0/10Tofacitinib, 11 mg1468.9504.7PSA (14)Methotrexate (3)Apremilast (1)HTN (5)PAD (1)CAD (3)Obesity/NASH (1)HLD (3)HCL (4)LTBI (1)SLE (1)NMSC (1)Hx of melanoma (1)9/1/3/11Total3770.1293.048/6/5/97This table describes the characteristics of the 37 elderly patients who were on Janus kinase (JAK) inhibitors from August 1, 2018, to August 1, 2023. The dosage of the JAK inhibitor prescribed is listed as milligrams daily. The reasons for treatment with a JAK inhibitor plus any concomitant systemic treatments are detailed. Additionally, the reason each patient was considered high-risk is listed.AA, Alopecia areata; AD, Atopic dermatitis; AE, adverse event; AU, alopecia universalis; CAD, coronary artery disease; CAS, carotid artery stenosis; COPD, chronic obstructive pulmonary disease; DLD, dyslipidemia; DM, dermatomyositis; DVT, deep vein thrombosis; GA, granuloma annulare; HCL, hypercholesterolemia; HLD, hyperlipidemia; HTN, hypertension; Hx, history; IBD, inflammatory bowel disease; JAK, Janus kinase; LTBI, latent tuberculosis infection; LV, livedoid vasculopathy; NASH, nonalcoholic steatohepatitis; NMSC, nonmelanoma skin cancer; PAD, peripheral arterial disease; PF, pemphigus foliaceus; PG, pyoderma gangrenosum; PSA; psoriatic arthritis; PSO, psoriasis vulgaris; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; T2DM, type 2 diabetes mellitus.∗ Total of "Reason for treatment" may not equal total of "No. of patients" on each therapy as several patients were prescribed 1 Janus kinase inhibitor for multiple diagnoses.† History of breast cancer (Lobular carcinoma in situ), patient in remission since 2015. Open table in a new tab This table describes the characteristics of the 37 elderly patients who were on Janus kinase (JAK) inhibitors from August 1, 2018, to August 1, 2023. The dosage of the JAK inhibitor prescribed is listed as milligrams daily. The reasons for treatment with a JAK inhibitor plus any concomitant systemic treatments are detailed. Additionally, the reason each patient was considered high-risk is listed. AA, Alopecia areata; AD, Atopic dermatitis; AE, adverse event; AU, alopecia universalis; CAD, coronary artery disease; CAS, carotid artery stenosis; COPD, chronic obstructive pulmonary disease; DLD, dyslipidemia; DM, dermatomyositis; DVT, deep vein thrombosis; GA, granuloma annulare; HCL, hypercholesterolemia; HLD, hyperlipidemia; HTN, hypertension; Hx, history; IBD, inflammatory bowel disease; JAK, Janus kinase; LTBI, latent tuberculosis infection; LV, livedoid vasculopathy; NASH, nonalcoholic steatohepatitis; NMSC, nonmelanoma skin cancer; PAD, peripheral arterial disease; PF, pemphigus foliaceus; PG, pyoderma gangrenosum; PSA; psoriatic arthritis; PSO, psoriasis vulgaris; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; T2DM, type 2 diabetes mellitus. Many patients had comorbidities (most commonly hyperlipidemia or hypertension). Other notable comorbidities observed included history of coronary artery disease, latent tuberculosis (treated with rifampin), bronchiectasis, nonmelanoma skin cancer, melanoma/melanoma in situ, cancer (breast, fallopian tube, and prostate [all in remission for ≥9 years]), hepatitis B, deep vein thrombosis, or stroke. Most patients experienced an improvement in disease after initiation of therapy (70.1%). Nine percent of patients experienced adverse events, several of which (depression, tremors/weakness, weight gain, and oral ulcers) required discontinuation of JAK-inhs and several that did not (herpes zoster and urinary tract infection) (Supplementary Table II, available via Mendeley at https://data.mendeley.com/datasets/9s4ytnznkm/1). This research was limited in design as it was a single-institution retrospective case series. However, despite higher age, comorbidities, and concomitant systemic medication use, most patients' disease was successfully treated without major adverse events. This supports the thought that systemic JAK-inhs should be considered in the elderly patient population. Additional studies with patients aged ≥65 years and treated with JAK-inhs are warranted. To conclude, systemic JAK-inhs seem to be a promising treatment for their approved dermatologic indications in the elderly population. Dr Khattri reports speaker honoraria from AbbVie, Eli Lilly and Company, Janssen Pharmaceuticals, and UCB; Advisory Board honoraria from Ichnos Sciences, Novartis, Sanofi/Regeneron, and UCB; speaker fees from Pfizer; consultant honoraria from Novartis; investigator grants/research funding (paid to the institution) from BMS, LEO Laboratories (LEO Pharma), and Pfizer; and consulting (unpaid) for Glenmark Pharmaceuticals. Author Hren has no conflict of interest to declare.