10.17.09 ~ 11.30 ~ Stein ~ Topical Therapy of Psoriasis and Atopic Dermatitis

10.17.09 ~ 11.30 ~ Stein ~ Topical Therapy of Psoriasis and Atopic Dermatitis

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Unformatted text preview: Disclosure Galderma Warner Chilcott Medicis Stiefel Linda Stein Gold, MD Linda Stein Gold MD Henry Ford Hospital Detroit, MI Vitamin D and psoriasis Psoriasis Calcitriol Betamethasone dipropionate 0.064% / Calcipotriene Calcipotriene 0.005% Topical Suspension Topical Suspension Tar 1979-1985 A direct action of vitamin D on skin cells was discovered 1985 … Shekito Morimoto described an 81-year old osteoporotic woman whose psoriasis was cured after 10 weeks of oral 1 alpha alpha-OH vitamin D3 vitamin 1989 Morimoto wrote a review article summarising his experience – Solution – Foam Available Vitamin D3 Agents Calcipotriene was approved for use in the US in 1994 Three topical vitamin D receptor modulators are available in Europe – Calcipotriene (calcipotriol*), tacalcitol, and Calcipotriene (calcipotriol tacalcitol and calcitriol1 calcitriol Calcipotriene cream: only topical vitamin D formulation currently available in the US Calcitriol ointment is a new option for psoriasis treatment in the United States Objective: Objective Evaluate efficacy safety of topical calcitriol Evaluate efficacy, safety of topical calcitriol 3 µg/g ointment in g/g ointment in subjects subjects with chronic mild-to-moderate plaque psoriasis mild-to839 patients in 2 randomized, double-blind, vehicle-controlled, doublevehicleparallelparallel-group clinical trials Design: Treatments: Calcitriol Calcitriol ointment or vehicle ointment BID for 8 weeks *Calcipotriol is the European nomenclature for calcipotriene. 1. British Association of Dermatologists. Available at: http://www.bad.org.uk/healthcare/guidelines/psorvitamin.asp. Accessed July 22, 2008. Lebwohl M, et al. J Drugs Dermatol. 2007;6:428-435. Treatment Treatment Success*: Study 1† 40 p=.009 Improvement in Psoriasis Lesions With Calcitriol Ointment After 8 Weeks Percentage of subjects p=.006 30 p=.002 20 p=.007 10 0 Week 2 Week 4 Week 6 Week 8 Vehicle Calcitriol 3µg/g ointment Baseline Week 8 *Success = Global Severity Score of clear/minimal †Study 1: n = 209 calcitriol ointment; 209 vehicle Lebwohl M, et al. J Drugs Dermatol. 2007;6:428-435. Reprinted with permission from Lebwohl M, et al. J Drugs Dermatol. 2007;6:428-435. Period 1 [1[1-90 days] N = 324 All All patients Baseline Baseline BSA*: <25% (N=253) Baseline BSA: 25% to 35% (N=71) • • • Period 2 [91[91-189 days] N = 285 3 (1.1%) 1 Period 3 [181[181-270 days] N = 233 3 (1.3%) 3 Period 4 [≥271 days] N = 140 1 (0.7%) 1 All Periods N = 324 10 (3.1%) 6 Investigator-Rated Global Severity of Psoriasis: 100 Proportion of Patients "Clear" or "Minimal" 75 Percent 4 (1.2%) 2 50 47.1 37.3 22.1 11.1 25 2 2 0 0 4 0 Period 1 1-3 mos Galderma R&D, data on file; final report, June 2004. Low overall incidence of hypercalcemia (3.1%) after 52 weeks Incidence of hypercalcemia similar regardless of BSA affected = One subject experienced 2 episodes of hypercalcemia Period 2 3-6 mos Period 3 6-9 mos Period 4 9-12 mos Use of topical calcitriol ointment for up to 52 weeks did not affect calcium homeostasis Betamethasone dipropionate 0.064% / Calcipotriene 0.005% Studies Significantly More Patients Had Controlled Disease With Combination Combination Scalp® (n=494) Betamethasone dipropionate in vehicle (n=531) % of patients Clear or Almost clear** 80 70 60 50 40 30 20 10 0 56% 46% † Study Number 0401 INT 0404 FR 0405 INT 0406 INT 0407 INT Details Phase II proof of concept study Study of the effect of BD/C Scalp on HPA axis and calcium metabolism Pivotal phase III study—4 arms study— Pivotal phase III study—3 arms study— Long-term phase III safety study Long- Duration 8 weeks 8 weeks 8 weeks 8 weeks 52 weeks 8 weeks doubledoubleblind followed by 44 weeks open label (52 weeks total) 8 weeks followed by 8 weeks of observation Number of Patients N=218 N=35 (58 screened) N=1505 N=1417 N=869 *p<0.001 Calcipotriene in vehicle (n=256) Vehicle (n=126) ‡p=0.016 †p=0.002 66% 70% 63% ‡ * 54% * 37% * 23% * 10% * 14% * 20% * 18% 0502 US Long-term phase III study in Hispanic Longand African American patients Phase III study comparing BD/C twiceScalp® with twice-daily Calcipotriene Scalp Solution N=177 0503 INT N=312 11 12 Week 2 Week 4 Week 8 **Clear or Almost clear = “Absence of disease” or “Very mild disease” by Investigators Global Assessment (IGA). Data on file. Warner Chilcott (US), LLC. 12 Significantly Significantly More Patients Treated With Combination Had Controlled Disease 80 Withdrawal of Patients Over Time 60 Number of patients withdrawing Taclonex Scalp® (n=207) Dovonex® Scalp Solution (n=105) *p<0.001 69% 60% 60 50 40 30 20 10 0 55% % of patients Clear or Almost clear† 70 50 Combinaton Calcipotriene ® 40 * 31% * 18% * 11% 30 20 10 Week 2 †Clear Week 4 Week 8 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 or Almost clear = “Clear” or “Minimal disease” according to Investigator’s Global Assessment (IGA). Data on file. Warner Chilcott (US), LLC. 13 13 n=417 n=350 n=427 n=299 CSR 407, Appendix XIV, pp 11-12, Table 48 Week n=336 n=265 14 Long-term phase III safety study Long- Safety Conclusions 100 Combinaton Calcipotriene % patients with “Satisfactorily controlled disease” using IGA** 90 Weak effect HPA- axis HPA– Combination use of BD/C gel on scalp + BD/C Ointment on body in extensive disease (60gms/ week) 80 Average weekly amount of drug used BD/C gel : 10.6 g/week Calcipotriene: 12.8 g/week 70 16% after 4 weeks and 18% after 8 weeks 18 60 50 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Calcium Metabolism – No clinically significant changes in serum or urine. Weeks *Used intermittently on an as-needed basis, for 52 weeks. **Satisfactorily controlled disease = “Absence of disease,” “Very mild disease,” or “Mild disease” by Investigator’s Global Assessment (IGA). 15 Data on file. Warner Chilcott (US), LLC. 15 16 History of LCD / Coal Tar-Based Psoriasis Therapy in the United States LCD Topical Solution Used to treat psoriasis alone and combined with UV light since 1920s Recognized by the FDA as safe and effective Recognized by the FDA as a safe and effective OTC OTC treatment for psoriasis, seborrheic dermatitis, and dandruff since 1970s Safety of medicinal tar was reviewed and rereaffirmed by the FDA in 2001 15% liquor carbonis distillate (LCD) Equivalent to 2.3% coal tar Aesthetically advanced Quick-drying, transparent vehicle 100 mL bottles with a “dab-on” “dabapplicator No patient contact with solution or lesions PSORENT® Package Insert. PASI 50 and PASI 75 achievers at week 12 Efficacy and Tolerability of a Cosmetically Acceptable 15% LCD Solution in the Treatment of Moderate Plaque Psoriasis: Percentage of Patients (%) LCD solution vs. calcipotriol cream for psoriasis 100 *P < 0.05 compared with calcipotriol LCD (n=27) 80 Calcipotriol (n=28) A Controlled Comparison with Calcipotriol Cream 67* 60 No patients in calcipotriol group achieved PASI 75 Alora-Palli MB, Perkins AC, Van Cott A, Kimball AB. 40 36 41* 20 0 0 PASI 50 Achievers PASI modified to exclude the head 1. Kimball AB et al. Poster P2403. AAD; Chicago, IL; July 30 – August 3, 2008. 2. Kimball AB et al. J Am Acad Dermatol. 2009; 60(3): AB174 (P3350). 3. Kimball AB et al. Submitted for publication. PASI 75 Achievers 1. Kimball AB et al. Poster P2403. AAD; Chicago, IL; July 30 – August 3, 2008. 2. Kimball AB et al. J Am Acad Dermatol. 2009; 60(3): AB174 (P3350). 3. Kimball AB et al. Submitted for publication. Relapse Rates During Follow-up Period LCD solution vs. calcipotriol cream for psoriasis 100 90 Percentage of Patients (%) Dermatology Life Quality Index Scores LCD solution vs. calcipotriol cream for psoriasis Moderate Impact 12.0 10.0 9.6 LCD (n=22) Calcipotriol (n=20) LCD 78 Calcipotriol 70 DLQI Score (Scale 0-30) 80 70 60 50 40 30 20 10 0 8.0 8.2 6.0 7.1 6.0 5.6 4.7 4.1 3.8 5.4 25* 4.0 2.0 No Impact 23* 2.6*† 0 4 8 Week 12 18 0.0 Follow-up Period PASI (Loss of PASI 50) *P < 0.05 compared with calcipotriol PGA (PGA worsening to baseline score) *P<0.01 compared to calcipotriol group at Week 18 †P<0.05 compared to Week 12 Kimball AB et al. J Am Acad Dermatol. 2009; 60(3): AB174 (P3350). Final data submitted for publication. Kimball AB et al. J Am Acad Dermatol. 2009; 60(3): AB174 (P3350). Final data submitted for publication. Patient Tolerability and Safety LCD solution vs. calcipotriol cream for psoriasis Clinical Response to Twice-Daily LCD Solution arm plaque Week 2 Week 0 Week 4 Both treatments were well tolerated Treatment-related AEs were comparable Treatment– LCD: moderate worsening of psoriasis (n=2); mild LCD: folliculitis (n=2), mild phototoxic reaction after unprotected sun exposure (n=1) – Calcipotriol: moderate worsening of psoriasis (n=2); Calcipotriol: moderate mild irritant contact dermatitis (n=1), mild burning pain after application (n=1) Week 8 Week 12 Week 18 (no therapy) LCD nonstinging/nonburning and nonirritating – Average “Very Good” score – Similar to calcipotriol Kimball AB et al. Final data submitted for publication. NeoStrata, data on file. Clinical Response to Twice-Daily LCD Solution arm plaque Week 0 Week 18 (no therapy) LCD plus NB-UVB reduces time to improvement of psoriasis vs. NB-UVB alone: a pilot study Jerry Bagel MD Jerry Bagel, MD Psoriasis Treatment Center of Central NJ J Drugs Dermatol. 2009;8(4):351-7. Week 12 Kimball et al. J Am Acad Dermatol. 2009; 60(3): AB174 (P3350). Patients with Clearance / Minimal Disease† NBNB-UVB + LCD vs. NB-UVB alone in psoriasis NBn = 12 Comparative Clinical Response NB-UVB + LCD vs. NB-UVB alone in psoriasis LCD+ NB-UVB NB-UVB *P=0.025 compared to UVB alone; **P<0.10 compared to UVB alone; Bagel J. J Drugs Dermatol. 2009; 8(4):351-7. †PGA=0 or 1 J Drugs Dermatol. 2009; 8(4):351-7. Week 0 Week 4 Week 8 15% LCD does not discolor bleached blond hair following 24 hour saturation Untreated Sample* Treated Sample* 24 hour Saturation in 15% LCD solution Coal Tar Foam 2% Aesthetically advanced Spreads easily, dries quickly Acceptable fragrance Comparable efficacy to Calcipotriene cream after 8 weeks Over the counter Tzaneva Tzaneva S, Honigmann H, Tanew A. Observer-blind, randomized, intrapatient comparison of a novel 1% coal tar preparation and Observercalcipotriol cream in the treatment of plaque psoriasis. B J Dermatol.2003;149:350-353 Dermatol.2003;149:350- . J Cosmet Dermatol. Accepted for publication, 2009. *Hair samples were dyed blond before the study Atopic Atopic Dermatitis Avoid triggers Skin Care Bathing Topical Corticosteroids Topical Immunomodulators Antihistamines Antimicrobials Topical Steroids FDA Approved for Pediatric Use Treatment Clobetasol propionate 0.05% foam Fluocinonide 0.1% cream Fluocinolone acetonide 0.01% oil Mometasone furoate 0.1% cream, ointment Fluticasone propionate 0.05% lotion Aclometasone dipropionate 0.05% cream, ointment Prednicarbate 0.1% cream, ointment Fluticasone propionate 0.05% cream Desonide 0.05% foam Desonide 0.05% gel FDA = US Food and Drug Administration. See approved labeling for individual products. Approved Age of Use ≥12 years ≥12 years ≥2 years ≥2 years ≥1 year ≥1 year ≥1 year ≥3 months ≥3 months ≥3 months Skin Care and Bathing Barrier Repair Creams Eltone Neosalus Mimyx Atoplicair Tetrix Epicerum Avoid environmental irritants Bathe 5-10 minutes, 1-2 times per day using mild 51cleansing agents – Hydrate – Cleanse – Improve penetration – Debried infected eczema Follow bathing by application of moisturizer/emollient within 3-5 minutes 3Use creams or ointments, avoid lotions Lynde C et al. J Cutan Med Surg. 2005 Jun 30 [Epub ahead of print]. Bleach Baths Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity Create a swimming pool environment Fill tub and add 1/4-1/2 cup common bleach 1/4– Modified Dakin’s solution with concentration of 0.005% Soak for 5-10 minutes 5Follow bathing by application of moisturizer/emollient or medication within 3-5 minutes 3Repeat 2-3 times per week 2- OBJECTIVES: – 1. Determine the prevalence of community-acquired MRSA colonization communityin patients with AD – 2. Determine if suppression of S aureus growth with sodium hypochlorite (bleach) baths and intranasal mupirocin treatment improves eczema severity. METHODS: A randomized, investigator-blinded, placebo-controlled study investigatorplacebo– 31 patients, 6 months to 17 years – moderate to severe AD and secondary bacterial infections. – All patients received oral cephalexin for 14 days and intranasal mupirocin ointment and sodium hypochlorite (bleach) baths (treatment arm) or intranasal petrolatum ointment treatment and plain water baths (placebo arm) for 3 months. Pediatrics. 2009 May;123 (5):e808-14 (5):e808- Pediatrics 2008 Oct; 122(4): 812-24 Treatment Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity RESULTS: – The prevalence of CA-MRSA in our study was CA 7.4% of our S aureus-positive skin cultures aureus 4% of our S aureus-positive nasal cultures was much lower than control aureus general population at Children's Memorial Hospital Chicago was much higher 75%75%-85% treatment group showed significantly greater improvement in EASI scores, treatment compared with the placebo group, at 1-month and 3-month visits. EASI scores for the head and neck did not decrease for patients in the treatment group – – Pediatrics. 2009 May;123 (5):e808-14 (5):e808- ...
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