Comparison between dupilumab and oral Janus kinase inhibitors in the treatment of prurigo nodularis with or without atopic dermatitis in a tertiary care center in Singapore

Abstract

To the Editor: Prurigo nodularis (PN) is a highly pruritic chronic skin disease with unknown pathophysiology. New evidence has suggested that antagonists of T-helper 2 cytokines and Janus kinase (JAK) inhibitors could be used as treatment.1Muller S. Bieber T. Stander S. Therapeutic potential of biologics in prurigo nodularis.Expert Opin Biol Ther. 2022; 22: 47-58Crossref PubMed Scopus (15) Google Scholar Dupilumab has recently been approved for treatment of PN but evidence remained limited.2Yosipovitch G.K.S. Mollanazar N. Ständer S. et al.Dupilumab significantly improves itch and skin lesions in patients with prurigo nodularis: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2).Br J Dermatol. 2023; 188: ii32-ii33Crossref Google Scholar,3Gael M. Adam T. Mariano-Bourin M. Bursztejn A.C. Efficacy of dupilumab in chronic prurigo and chronic idiopathic pruritus: a systematic review of current evidence and analysis of response predictors.J Eur Acad Dermatol Venereol. 2022; 36: 1541-1551Crossref PubMed Scopus (9) Google Scholar reports of oral JAK-inhibitors for PN are also uncommon. We therefore aim to assess and compare the treatment efficacy of dupilumab and oral JAK-inhibitors for PN with or without atopic dermatitis (AD) in a real-world clinical cohort. Patients diagnosed having PN (with or without AD) by dermatologists and received either dupilumab or oral JAK-inhibitors at a tertiary skin center in Singapore from 01 January, 2018 to 30 September, 2022 were analyzed. Demographics, comorbidities, treatment regimen, prior treatment details, body surface area (BSA), Worst Itch Numerical Rating Scale (WI-NRS), and retrospective charting of Investigator’s Global Assessment for PN-Stage (IGA PN-S) according to number of nodules were recorded. Response was defined as a WI-NRS reduction of ≥4 or IGA PN-S score of 0 or 1 assessed at Week 12 to 16.2Yosipovitch G.K.S. Mollanazar N. Ständer S. et al.Dupilumab significantly improves itch and skin lesions in patients with prurigo nodularis: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2).Br J Dermatol. 2023; 188: ii32-ii33Crossref Google Scholar Subjective improvements were documented (Table I).Table IComparison of prurigo nodularis patients treated with dupilumab or oral JAK inhibitorsDupilumab (n = 36)Oral Jak inhibitors (n = 13)P valueAge (mean, years)42.7 ± 20.653.7 ± 16.4.087Female (%)27.861.5.045Race (%) Chinese88.9100.455 Malays8.30 Indians2.80With atopic dermatitis (%)77.869.2.708Atopy history (%)63.930.8.040Duration of disease (years)14.8 ± 12.114.6 ± 7.37.954Previous treatments (%) Potent topical steroids1001001.00 Oral prednisolone pulses94.41001.00 Intralesional steroids22.230.8.539 Liquid nitrogen16.715.4.915 Phototherapy (NBUVB, UVA1)63.984.6.293 Methotrexate27.869.2.009 Ciclosporin33.384.6.001 Azathioprine8.376.98.00E-06 Mycophenolate mofetil5.646.2.003 Dupilumab-23.1- Others (eg, thalidomide, aprepitant, apremilast, adalimumab, acitretin, isotretinoin)8.353.8.002Duration of treatment (weeks)40.3 ± 39.818.5 ± 11.1.005Time to first response (weeks)10.7 ± 13.43.65 ± 2.27.004Baseline BSA∗BSA: Body surface area of prurigos and dermatitis (if any); NBUVB: narrow band UVB. (%)19.2 ± 20.310.7 ± 4.57.023BSA∗BSA: Body surface area of prurigos and dermatitis (if any); NBUVB: narrow band UVB. at Week 12-16 (%)7.31 ± 10.55.92 ± 4.15.648Baseline itch score†Worst Itch Numerical Rating Scale. (out of 10)7.39 ± 1.208.46 ± 1.20.008Itch score†Worst Itch Numerical Rating Scale. at Week 12-16 (out of 10)3.31 ± 2.324.46 ± 2.15.123Itch score†Worst Itch Numerical Rating Scale. reduction of ≥ 4 at Week 12-16 (%) (n = 42)6058.3.921Investigator's Global Assessment for PN-stage (IGA PN-S) at baseline (%).846 0 (no nodules)00 1 (1-5 nodules)5.60 2 (6-19 nodules)5.67.7 3 (20-99 nodules)7576.9 4 (over 100 nodules)13.915.4IGA PN-S at Week 12-16 (n = 42) (%).381 0 (no nodules)108.3 1 (1-5 nodules)3016.7 2 (6-19 nodules)43.333.3 3 (20-99 nodules)16.741.7 4 (over 100 nodules)00IGA PN-S of 0 or 1 (%) at Week 12-16 (n = 42) (%)40.025.0.485Adverse effects (%)22.223.1.950Patients’ subjective improvement (%)‡Subjective improvements in itch or flattening of nodules.72.276.9.742 AD flare (%)2.87.7.464 Eye symptoms (%)11.10.562 Skin infections (Herpes, impetigo) (%)2.815.4.168 Head and neck dermatitis (%)5.601.00P value of less than .05 are bold and italic.∗ BSA: Body surface area of prurigos and dermatitis (if any); NBUVB: narrow band UVB.† Worst Itch Numerical Rating Scale.‡ Subjective improvements in itch or flattening of nodules. Open table in a new tab P value of less than .05 are bold and italic. Thirty-six PN patients received dupilumab (300 mg fortnightly) and 13 patients had oral JAK-inhibitors. Ten patients had baricitinib (2-4 mg daily) while the remaining 3 had upadacitinib (15 mg daily). Overall, mean age of patients was 45.6 ± 20.0 years. Majority were male (63.3%) and ethnic Chinese (91.8%). Most PN cases (75.5%) also had concurrent AD. Patients on dupilumab were significantly more likely to have atopy but less likely to have previous oral immunosuppressants than those on JAK-inhibitors (Table I). While baseline BSA and itch scores differed, both groups achieved similar response targets. At week 12-16, the ≥4-point reduction in WI-NRS of the dupilumab group was achieved by 60.0%, versus 58.3% in the JAK-inhibitors group (P = .921). An IGA PN-S score of 0 or 1 was achieved by 40.0% in the dupilumab group versus 25.0% in the JAK-inhibitors group (P = .485). However, those on oral JAK-inhibitors have a faster first response than dupilumab (3.65 ± 2.27 vs 10.7 ± 13.4 weeks; P = .004), after adjusting for confounders (P = .042). Both have similar adverse effects risk, but disease flare and skin infections seemed more common in the JAK-inhibitors group. Our study showed good clinical improvements in itch and nodules for both treatments. These responses were higher than the LIBERTY-PN-PRIME trials which had 40.5% patients having a ≥4-point reduction in itch scores and 28.8% patients achieving IGA-PN-S score of 0 or 1 at Week 12.2Yosipovitch G.K.S. Mollanazar N. Ständer S. et al.Dupilumab significantly improves itch and skin lesions in patients with prurigo nodularis: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2).Br J Dermatol. 2023; 188: ii32-ii33Crossref Google Scholar This could be attributed to concurrent use of potent topical or intralesional steroids. This study is among the first to compare dupilumab with oral JAK-inhibitors in treating PN. It is, however, limited by a small sample size and its retrospective nature. Further insights could be extrapolated from recent head-to-head studies of dupilumab and JAK-inhibitors in the treatment of AD (Heads Up and JADE COMPARE trials).4Blauvelt A. Teixeira H.D. Simpson E.L. et al.Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial.JAMA Dermatol. 2021; 157: 1047-1055Crossref PubMed Scopus (195) Google Scholar,5Bieber T. Simpson E.L. Silverberg J.I. et al.Abrocitinib versus placebo or dupilumab for atopic dermatitis.N Engl J Med. 2021; 384: 1101-1112Crossref PubMed Scopus (193) Google Scholar Oral JAK-inhibitors were found be more superior than dupilumab in treatment of AD.4Blauvelt A. Teixeira H.D. Simpson E.L. et al.Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial.JAMA Dermatol. 2021; 157: 1047-1055Crossref PubMed Scopus (195) Google Scholar,5Bieber T. Simpson E.L. Silverberg J.I. et al.Abrocitinib versus placebo or dupilumab for atopic dermatitis.N Engl J Med. 2021; 384: 1101-1112Crossref PubMed Scopus (193) Google Scholar However, more studies could be performed to compare efficacy of these agents in PN patients only. None disclosed.

Topics & Concepts