Hidradenitis and other inmune mediated skin diseases. Dr. Antonio Martorell Hospital de Manises, Valencia

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1 Hidradenitis and other inmune mediated skin diseases Dr. Antonio Martorell Hospital de Manises, Valencia

2 Hidradenitis y dermatitis atópica

3 a Pictures courtesy of Antonio Martorell MD Ph.D

4 Topical Resorcinol 15%

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6 Hidradenitis F11: advanced management strategies for HS Zinc, adjuvant therapy at dose of 90 mg Campanati A et al. Skin Apped Disord 2017 **Hiperhidrosis control and improvement in HS Endocrinologically active drugs Few studies *Spironolactona. Only 20 patients published. J Dermatol 2015 Lee y Fischer No evidence *Biguanides (Metformin) Indicated as coadjuvant, in obese or diabetic cases. Arun, Clin Expe 2009 **Non as single therapy

7 Adalimumab, first line therapy

8 HiSCR rate by week of treatment with adalimumab HiSCR rate increased from baseline to Week 48 in both populations and was maintained to Week 108 Patients, % Primary Analysis N a. Weeks include PIONEER I or II + the OLE, listed consecutively Weeks a : n/n LOCF As Observed ADAe n w N PRR n PRR, partial responder and responder; ADAew, adalimumab every week; LOCF, last-observation-carried-forward Zouboulis C, et al. Presented at the 75 th Annual Meeting of the AAD. Orlando, Florida, March 3 7, ADAew Population PRR Population Safety profile of long-term weekly adalimumab was consistent with the known safety profile and no new safety risks were identified

9 What to do when anti TNFs stop working? Titrate drug dose and frequency Check for anti TNF neutralizing antibodies Bacterial culture: antimicrobials Change to another agent

10 Infliximab en HS Design: Prospective, double blind, 8-week study 38 subjects randomised IFX n=15; 5 0, 2, 6, 14, 22 weeks Pbo n=23; cross 8 weeks to IFX regimen Observational, non treatment until 52 weeks Primary outcome measure: 50% reduction from baseline HSSI Additional results: Statistical, clinically significant improvement DLQI, VAS, ESR, CRP Many patients withdrew from observational phase to continue anti TNF tx Limitations: Single-centre, single-hcp study Non validated endpoint used

11 Anakinra en HS Double blind RCT Patients with Hurley stage II or III HS were randomized to placebo (n=10) or anakinra (n=9) for 12 weeks, followed by another 12 weeks of follow-up *Off-label use; RCT, randomized control trial; wk, weeks; PBO, placebo; HiSCR, Hidradenitis Suppurativa Clinical Response. Tzanetakou V, et al. JAMA Dermatol. 2016;152:52 59.

12 Patients (%) Ustekinumab y HS Ustekinumab induced moderate to significant reductions in objective HS activity Patients (%) at Week 40 with improvement in mss/mhslasi Open-Label, 40-week study of Ustekinumab (n=17) 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 35% mss 47% *Off-label use; mss, modified Sartorius scale; mhslasi, modified hidradenitis suppurativa-lesion area and severity index. Blok JL, et al. Br J Dermatol. 2016;174: % mhslasi 35% 50% improvement (i.e. significant improvement) 25 50% improvement (i.e. moderate improvement) ØmSS reduction: 46% ØmHSLASI reduction: 26% Analysis does not include nonresponders. Moderate improvement probably also includes patients with significant improvement (>25%)

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14 Surgical recurrence Recurrence is almost inevitable following incision and drainage procedures 1-5 A systematic review/meta-analysis of surgical approaches in HS (22 articles) 6 Wide excision associated with the lowest rates of recurrence Surgical technique Average recurrence rate (%) Wide excision 13 Primary closure 15 Flaps 8 Grafting 6 Local excision 22 Deroofing Danby FW, et al. J Am Acad Dermatol. 2015;73(5 Suppl 1):S62 5; 2. Ellis, LZ. Dermatol Surg. 2012; 38: ; 3. Balik E, et al. World J Surg 2009;33: ; 4. Kohorst JJ, et al. Dermatol Surg. 2016;42: ; 5. Ritz JP, et al. Int J Colorectal Dis. 1998;13: ; 6. Mehdizadeh A, et al. J Am Acad Dermatol. 2015;73(Suppl 5):S70 S77.

15 Combination of Surgery and Biologics Comparison of patients (N=21) undergoing combined surgery + biologic therapy vs. surgery alone 1 Surgery + biologics associated with: Significantly lower rates of recurrence/disease progression (18% vs. 50% for surgery alone; P<0.001) Longer disease-free interval (18.5 vs. 6 months; P<0.001) Retrospective case series (N=24; HS staging II or III) of patients undergoing treatment with infliximab + surgery (deroofing, small/large incisions) to remove remaining fistulas or sinuses 2 At 50 months, 37% of patients treated with infliximab + adjuvant surgery were disease-free vs. 13% of patients treated with infliximab alone 1. DeFazio MV, et al. Ann Plast Surg. 2016;77:217 22; 2. Van Rappard DC & Mekkes JR. Br J Dermatol. 2012;167:

16 Emma Gutman MD,Mount Sinai Hostpial

17 LT CD4 y CD8 activation in DA Emma Gutman MD,Mount Sinai Hostpial

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19 Is AD a single disease across the spectrum Paller AS. JACI 2016

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22 Dermatitis atópica, enfermedad sistémica

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36 Inflammatory conjunctivitis

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39 Conclusions in AD Traditional systemics are effective for AD but take a close moritoring Many biologics for AD in Phase 3 Dupilumab, safe and effective option today Oral JAK inhibitors, the future in AD