Incorporating Biologics Into Your Practice Jeffrey M. Sobell MD Tufts University School of Medicine SkinCare Physicians Ora Clinical Research Disclosure Of Relationships With Industry Amgen AbbVie Celgene Eli Lilly Janssen Merck Novartis Regeneron Sun Pharma Jeffrey M. Sobell MD DISCLOSURES Investigator (grant) Investigator (grant); Speaker (honoraria) Investigator (grant) Consultant Objectives Review the indications for using biologics in dermatology Understand criteria for choosing an appropriate biologic Explore how to start and follow a patient on biologics Incorporating Biologics Into Your Practice When to use biologics How to choose a biologic How to get a patient started How to follow patients over time Biologics In Dermatology Biologics In Dermatology: When Are They Appropriate? Psoriasis TNF-α antagonists Etanercept Adalimumab Infliximab IL-12/23 antagonists Ustekinumab IL-17A antagonists Secukinumab Ixekizumab Hidradenitis Suppurativa TNF-α antagonists Adalimumab Moderate-severe Psoriasis Topicals Non-topicals Phototherapy Conventional systemic meds Oral small molecules Biologic agents Hidradenitis Suppurativa Moderate-severe disease Base on active inflammatory lesions 1
Incorporating Biologics Into Your Practice When to use biologics How to choose a biologic How to get a patient started How to follow patients over time Biologics: How To Choose Step 1: Do no harm: know the safety profile of each biologic Step 2: Evaluate for co-morbidities Step 3: Consider concomitant medical issues Step 4: Choose best method of administration Step 1: Safety Profiles Of Biologics* Biologics: How To Choose TNF-α antagonists Serious infection Malignancy Demyelinating disease Hepatitis B Hematologic Lupus like syndrome Live vaccines IL-12/23 antagonists Serious infection Malignancy Reversible posterior leukoencephalopathy syndrome Live vaccines IL-17 antagonists Serious infection Hypersensitivity Live vaccines Step 1: Do no harm: know the safety profile of each biologic Step 2: Evaluate for co-morbidities Step 3: Consider concomitant medical issues Step 4: Choose best method of administration *selected safety considerations All but Ixekizumab currently FDA approved for PsA Favor: TNF-α antagonists > IL- 17 antagonists > IL-12/23 antagonists 2
How Do ACR Responses Compare In The Therapeutic Environment? Patients (%) 100 90 80 70 60 50 40 30 20 10 0 15 57 39 23 13 50 37 9 16 54 41 27 Week 24 ACR responses 42 23 25 23 12 50 28 14 ACR20 placebo ACR20 ACR50 ACR70 37 20 13 15 11 54 35 20 58 40 30 30 ADA ETN IFX UST 45 mg UST 90 mg APR 30 mg SKB 300 mg IXE q4w IXE q2w 1 2 3 4 4 5 6 7 7 (ADEPT) (PsA Pivotal Study) (IMPACT 2) (PSUMMIT 1) (PALACE 1) (FUTURE 2) (SPIRIT P1) 23 62 47 34 Coronary artery disease Favor TNF-α antagonists Metabolic syndrome Obesity Hypertension Diabetes Dyslipidemia Data are not based on head-to-head trials, and are presented for illustrative purposes. They cannot be directly compared. 1. Mease PJ, et al. Arthritis Rheum 2005;52:3279 89; 2. EMA: Enbrel (etanercept) SmPC; Jan, 2016; 3. Antoni C, et al. Ann Rheum Dis 2005;64:1150 7; 4. McInnes IB, et al. Lancet 2013;382:780 9; 5. Kavanaugh A, et al. Ann Rheum Dis 2014;73:1020 6; 6. McInnes IB, et al. Lancet 2015;386:1137 46; 7. Mease P, et al. AAD 2016, P2515 CAD Metabolic syndrome Obesity Disfavor: etanercept Hypertension Diabetes Dyslipidemia Patients Above 200 lbs Respond Less Favorably To Etanercept, Regardless Of Dose % of patients achieving PASI 75 Etanercept PASI 75 response at 12 weeks by dose and weight 60 50 40 30 20 10 0 Gordon et al. J Am Acad. Derm. 2006;54:S101 3 Patients less than ~200 lbs (<89.4 kg) Patients ~200 lbs and above (>89.4 kg) 3 55 n=193 n=221 n=195 n=162 n=218 n=197 Placebo Etanercept Etanercept 50 mg BIW 50 mg weekly 43 41 25 Favor: adalimumab, infliximab, ustekinumab Caution: IL-17 antagonists Secukinumab Pooled Subanalysis Of 10 Studies In Moderate-Severe Psoriasis Evaluating Exacerbation Of Inflammatory Bowel Disease Entire treatment (randomization to Week 52) after induction, subjects in Phase 3 studies (>80% all subjects) received SKB q4w or RAN from Weeks 12 to 48 a, or ETN weekly from Weeks 12 to 51 Exposure-adjusted incidence of IBD during the entire treatment period SKB 300 mg a (n=1410) SKB 150 mg a SKB any dose b PBO ETN c (n=1395) (n=3430) (n=793) (n=323) Duration of exposure, days 305.0 ± 101.67 299.0 ± 103.89 290.1 ± 110.53 92.7 ± 57.05 331.9 ± 89.70 (mean ±SD) Incidence overall, n (%) IBD 3 (0.26) 4 (0.35) 9 (0.33) 0 1 (0.34) Crohn s disease 0 2 (0.18) 3 (0.11) 0 0 Ulcerative colitis 2 (0.17) 2 (0.18) 4 (0.15) 0 1 (0.34) Anal fistulad 1 (0.08) 0 1 (0.04) 0 0 Sclerosing cholangitis d 0 0 1 (0.04) 0 0 Incidence in the subgroup with prior history of IBD, n (%) [95% CI] 15 14 39 Subjects with prior IBD history, n 11 0 IBD overall 0 (0) 2 (18.76) 3 (10.53) 0 (0) [0.00 30.90] [2.27 67.78] [2.17 30.76] [0.00 139.33] Crohn s disease 0 (0) 1 (9.28) 2 (6.99) 0 (0) [0.00 30.90] [0.23 51.70] [0.85 25.25] [0.00 139.33] Ulcerative colitis 0 (0) 1 (9.23) 1 (3.47) 0 (0) [0.00 30.90] [0.23 51.42] [0.09 19.32] [0.00 139.33] a Includes subjects from Phase 3 studies only who received the specified SKB dose (300 or 150 mg) regardless of dosing interval (ie, q4w, RAN); PBO subjects who were re randomized to SKB at Week 12 are also included, and had an induction period with weekly SKB doses from Weeks 12 to 16; b Includes subjects from Phase 2 and 3 studies who received any dose of SKB; c ETN data are from one pivotal Phase 3 trial, FIXTURE; d Anal fistula and Sclerosing cholangitis are not true IBD, they were retrieved because of the broader search criteria applied Ward N, et al. AAD 2014, P8233 RAN, retreatment as needed 3
Warning in TNF-α antagonist label Advise caution with all biologics Biologics: How To Choose Step 1: Do no harm: know the safety profile of each biologic Step 2: Evaluate for co-morbidities Step 3: Consider concomitant medical issues Step 4: Choose best method of administration Step 3: Consider Concomitant Medical Step 3: Consider Concomitant Medical Caution: all biologics Tuberculosis TB testing mandatory before initiation of all 6 approved biologics Hepatitis Hep C: Favor: TNF-α antagonists Hep B: Caution: TNF-α antagonists Deep fungal infections Caution: TNF-α antagonists HIV Favor: TNF-α antagonists Step 3: Consider Concomitant Medical Caution: TNF-α antagonists 4
Step 3: Consider Concomitant Medical Avoid: TNF-α antagonists Step 3: Consider Concomitant Medical Advise caution: all biologics Cutaneous SCC Caution: TNF-α antagonists Solid tumors Depends on type, severity and duration Risk/benefit discussion Biologics: How To Choose Step 1: Do no harm: know the safety profile of each biologic Step 2: Evaluate for co-morbidities Step 3: Consider concomitant medical issues Step 4: Choose best method of administration Method Of Administration And Maintenance Dose Frequency Self administration: SQ Etanercept: weekly Adalimumab: every other week Secukinumab: monthly Ixekizumab: monthly In-office administration Ustekinumab*: every 3 months (SQ) Infliximab: infusion every 8 weeks (IV) SQ: subcutaneous IV: intravenous * Approved for self administration as well Incorporating Biologics Into Your Practice When to use biologics How to choose a biologic How to get a patient started How to follow patients over time Biologics: Getting Started workup 5
Biologics: Getting Started Biologics: Getting Started Symptoms Prior therapies PGA (Physicians Global Assessment) BSA (Body Surface Area) Skin cancer screen workup workup Complete blood count Chemistry panel Liver function tests TB screen Hepatitis panel HIV test Β-hcg (if appropriate) Biologics: Getting Started Biologics: Getting Started workup Company brochures National Psoriasis Foundation website (www.psoriasis.org) Injection training option for patients through company sponsored health care providers workup The most frustrating part! Company resources can be helpful Incorporating Biologics Into Your Practice When to use biologics How to choose a biologic How to get a patient started How to follow patients over time 6
point for evalution: generally at 12 weeks Both patient and physician should be satisfied PQRS criteria PGA 0,1 BSA < 3% Every 3-6 months Ascertain compliance with therapy Constitutional Infections Neurologic Cardiovascular Gastrointestinal every 6-12 months : Every 3-6 months every 6-12 months Annual tuberculosis screen General wellness labs every 6-12 months Biologics: Switching Therapy Primary lack of efficacy Secondary loss of efficacy Side effects Infection Paradoxical worsening of psoriasis Lupus like syndrome Discontinuation without switching New malignancy Sepsis Pregnancy? 7
Conclusions 6 approved biologics for psoriasis, 1 for hidradenitis suppurativa Important to know biologic attributes and PMH to optimize patient selection Utilize resources from pharmaceutical companies to aid in patient education, injection training and access to therapy Routine follow up visits to assess ongoing safety and efficacy over time 8