PATIENT CENTRIC MEASURES IN HTAs FOR AUTOIMMUNE DISEASES

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1 PATIENT CENTRIC MEASURES IN HTAs FOR AUTOIMMUNE DISEASES Monday, November 12, 2018 Carlijn Hintzen, Rianne Ernst, Arun Chhikara, Cristina Ivanescu, Anke van Engen, Mary New Copyright 2018 IQVIA. All rights reserved. Autoimmune diseases are mostly chronic, non-fatal and treatment should focus on alleviating symptoms Psoriasis Chronic disease with flares Symptoms include Arthritis Red patches of skin covered with thick scales Small scaling spots (common in children) Dry, cracked skin that may bleed Itching, burning or soreness Thickened, pitted or ridged nails 1 2 Inflammation of one or more joints Main symptoms are joint pain, stiffness others include: Pain Stiffness Swelling Redness Decreased range of motion Systemic lupus erythematosus (lupus) Systemic autoimmune disease with episodes, or flares Most distinctive sign is a facial rash shaped like wings of a butterfly; other symptoms include: Fatigue, fever, joint pain, stiffness and swelling, photosensitivity, Raynaud's phenomenon, shortness of breath, chest pain, dry eyes, headaches, confusion and memory loss Inflammatory bowel disease Ulcerative colitis long-lasting inflammation and sores in the colon and rectum Crohn s disease inflammation of the lining of the digestive tract Symptoms common to both disorders include: (Severe) diarrhea, fever and fatigue, abdominal pain and cramping, blood in your stool, reduced appetite and unintended weight loss Sources:

2 Clinical Outcome Assessments (COAs) are used to measure the patient experience which is important to show treatment benefit Patient Reported Outcome (PRO) A measurement that comes directly from the patient Clinician Reported Outcome (ClinRO) An assessment determined by a trained medical professional Composite Measure (CM) A measurement that integrates two or more individual measures Performance Rated Outcome (PerfO) A measurement based on a task(s) performed by a patient Observer Reported Outcome (ObsRO) An assessment determined by an observer (i.e., a nonclinician, such as a teacher or caregiver). *All definitions are based on the definitions determined by PROQOLID 3 To research the impact of COA use in HTA submissions, submissions for HTA agencies between are analysed Relevant HTA submissions are identified via the use of data from the HTA Accelerator platform. Research scope included: auto-immune diseases: lupus,, arthritis, Crohn s disease, ulcerative colitis HTA agencies: HAS, G-BA, IQWiG, NICE, SMC HTA reports published between To prevent skewed data, the scope was further limited to: Included assessment types: original, resubmission, extension of indication Analysis The 13 submission in scope are analysed on inclusion of COA data in the submission. Analysis included if COA data are submitted, which COA type is submitted, if COA data are accepted by HTA agencies and if we see different trends between the auto-immune diseases

3 All HTA submissions including clinical data include COA data, the submission clinical data differs per disease area % HTA submissions including COA data over time (n=12) Inclusion of COA data per indication (n=113) % 77% % 16 17% 13% 78% % 70% % % 92% % 6% 7% % 97% % 1% 80% 22 9% 86% Arthritis Psoriasis % 6 83% SLE 20% 80% CD UC no data submitted unknown submission of data submission included COA data In >9% the COA was a primary endpoint in the clinical trial To prevent double-counting only assessments by IQWiG are included for each drug. One assessment by G-BA for off-label use of a drug as this was not assessed by IQWiG The percentage of different COA types differs per disease, as different COAs are used for each disease Types of COAs submitted per indication 6% 92% 96% 9% 60% 17% 11% % 0% Arthritis (2) Psoriasis (19) Systemic Lupus Erymathosus (SLE) () 7% 80% 80% 0% 13% 0% 0% Crohn s disease (CD) (8) Ulcerative colitis (UC) () IQVIA HTA Accelerato HTA submission in auto-immune disease for HTA agencies published between 2011 and 2017 [data extraction October 2018] To prevent double-counting only assessments by IQWiG are included for each drug. One assessment by G-BA for off-label use of a drug as this was not assessed by IQWiG 6 3

4 For all disease areas different COAs are used in clinical trials, this is guided by recommendations by regulators Top 3 of submitted COAs #1 COA #2 COA #3 COA EMA guideline compliant Arthritis (2) ACR HAQ DAS-28 Crohn s disease (8) CDAI (Crohn s) IBDQ ~ Psoriasis (19) PASI BSA SLE () BILAG Index SELENA- SLEDAI PhGA Ulcerative colitis () Mayo Score IBDQ EQ-D ~ Composite ClinRO PRO Disease-specific COA Generic COA Compliant ~ measure Historically compliant 7 COA data are used by IQWiG to determine a product s morbidity and HRQoL benefit rating, however not all COA data is evaluated Drug Indication* COA for morbidity Cosentyx Cosentyx resubm Taltz Olumiant Xeljanz Kevzara Kyntheum Active rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis PASI; Symptom NRS; EQ-D VAS PASI; NAPSI PASI; Itch NRS; NAPSI; VAS; EQ-D VAS PASI; VAS NAPPA-Clin; EQ-D VAS DAS-28; SDAI; VAS; EQ-D VAS; FACIT-F; HAQ-DI CDAI; SDAI; DAS-28; VAS; FACIT-F; HAQ-DI; MOS Sleep Scale CDAI; SDAI; DAS-28; VAS; EQ-D VAS; FACIT-F; HAQ-DI COA for HRQoL ; ; ; Morbidity rating HRQoL rating Safety IQWiG rating G-BA rating Comments PASI NRS Based on the symptoms data IQWiG concludes a lower rating for patients with previous PASI treatment whilst G-BA concludes a higher rating PASI PASI PASI; VAS Non-PRO CDAI, SDAI, DAS-28, HAQ-DI CDAI, SDAI, DAS-28 CDAI, SDAI, DAS-28 HAQ- DI HAQ- DI VAS VAS PASI; NAPSI; PSI PASI G-BA weighed the no benefit for symptoms and more harm in side effects more than IQWiG IQWiGs addendum changed the rating from lesser benefit to no added benefit IQWiG concluded that no significant differences were seen for all endpoints IQWiGs addendum changed the rating from lesser benefit to no added benefit IQWiG concluded that no significant differences were seen for all endpoints IQWiG split the group dependent on remission being a therapy goal. GB-A did not make this split, therefore they have provided the same rating for both groups. IQWiG benefit rating Major added benefit Considerable added benefit Minor added benefit Non-quantifiable added benefit No added benefit Major more harms or less benefit Considerable more harms Minor more harms Non-quantifiable more harms *All indications are moderate to severe Change after addendum 8 4

5 All analysed agencies use submitted COA data in their HTA decisions, as these instruments are well-known and established The morbidity endpoint category is based on physical status (HAQ-DI), as well as statistically based on low disease activity (SDAI 11) and shows a significant benefit for baricitinib + MTX over the ACT G-BA on Olumiant There is an indication of considerable added benefit for morbidity (remission [PASI 0]). For HRQoL, there was an indication of a minor added benefit of ixekizumab compared to ustekinumab at the outcome "" IQWiG on Taltz Clinical experts explained that there is now a move towards more objective assessment of disease activity. The committee accepted that the use of the CDAI was acceptable given its historic use in assessing response to other biological treatments NICE on Stelara The primary outcome was ACR20 response, which is a validated outcome in rheumatoid arthritis SMC on Inflectra The choice of ACR 20 as the main co-criterion for judging efficacy can be discussed because it represents a very modest objective (improvement of 20% of signs and symptoms in relation to baseline) HAS on Kevzara 9 COA data of which the use is increased over the years, is evaluated by agencies and can be a differentiator for products Frequency of COA data All submissions in scope which submitted data, included COA data as part of the clinical data package In >9% of the submitted clinical trials COA data was the primary endpoint Type of COA data The distribution of COA types used differs per disease but for all diseases the most frequently used COA is either a composite measure or ClinRO, used COAs are in line with the disease guidance from regulators Acceptance of COA data COA instruments are generally accepted as these are well-known, established and disease guidance Recommendations are driven by the significance of the results measures with COAs

6 QUESTIONS 11 6