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THREE-MONTHLY LONG-ACTING ANTIPSYCHOTIC THERAPY RESULTS IN A BETTER TREATMENT CONTINUITY COMPARED TO A ONE-MONTHLY OR BI-WEEKLY TREATMENT IN SCHIZOPHRENIA Tedouri F1, Denee TR2, Malfait B3, Van Impe K2 1Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium, [email protected]; 2Janssen-Cilag BV, Doctor Paul Janssenweg 150, 5026 RH Tilburg; 3Janssen-Cilag NV, Antwerpseweg 15-17, 2340 Beerse, Belgium. INTRODUCTION AND OBJECTIVE RESULTS Schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. Typical and atypical long-acting antipsychotic therapies that aim to improve symptoms of illness and patient’s health-related quality of life (HRQL) are widespread available. Treatment continuity is a key element to improve treatment outcomes in schizophrenia patients. Treatment discontinuation has been determined as a strong indicator of relapse1,2,3,; with each relapse having a clinical and economic impact4, due to the high cost of hospitalizations5. De Hert et al. demonstrated in a recent review that patients who were continuously treated with an antipsychotic had three times lower relapse risk than those who follow an intermittent treatment strategy1. The objective of this research is to investigate the impact of a threemonthly long-acting antipsychotic therapy (LAT) versus one-monthly and bi-weekly therapies, using real-world evidence (RWE) from paliperidone palmitate one-monthly (PP1M) and risperidone microspheres (RM) LAT in Belgium and the Netherlands. Treatment continuity is higher for three-monthly LAT versus PP1M and RM. Percentage increase in time on treatment in the base case scenario for three-monthly LAT was 28% versus PP1M and 57% versus RM in Belgium, and 15% versus PP1M and 46% versus RM in the Netherlands. In the additional scenario, the percentage increase in time on treatment for three-monthly LAT was 32% versus PP1M and 61% versus RM in Belgium, and 18% versus PP1M and 50% versus RM in the Netherlands. Figure 3. Mean days on treatment in 1 year , ∆ = % increase in time on treatment METHODS RWE studies assessing the treatment continuity in patients with schizophrenia in Belgium and the Netherlands were used to investigate the impact of a three-monthly LAT on time on treatment versus onemonthly and bi-weekly. These RWE studies were developed using the IMS LifelinkTM Treatment Dynamics database in both countries6,7. Four cohorts including patients who were treated in outpatient settings were defined, two cohorts including patients treated with paliperidone palmitate one-monthly (n=813) and risperidone microspheres (n=568) in Belgium and two cohorts including patients treated with paliperidone palmitate one-monthly (n=524) and risperidone microspheres (n=411) in the Netherlands. The mean treatment duration in the first 12 months for PP1M and RM was determined by calculating the area under the Kaplan-Meier curve of patients who were still on treatment8.A half-cycle correction was applied to avoid overestimation of time on treatment9. Simulation of 90-day therapy interval: PP1M estimates were used to simulate time on treatment of a threemonthly interval antipsychotic. Two scenarios, a base case and an additional scenario were formulated to show the sensitivity of the results when using different assumptions. The base case scenario was built on the theoretical assumption that patients treated with three-monthly LAT could only discontinue after three months of every administration and it was assumed that the proportion of patients who were still on treatment on the three-monthly LAT drops after every three months to the level of PP1M (figure 1). In the additional scenario, it was assumed that the proportion of patients who were on three-monthly treatment drops after three months to the level of patients who were on PP1M after one month and then mimics the remainder of the PP1M survival curve (figure 2). The mean number of treatment days per cohort and per country were calculated accordingly as shown in figure 3. Figure 1. Time on medication in Belgium as described in the base case scenario DISCUSSION Longer drug coverage periods can reduce the number of therapy administrations and results in an improved treatment continuity reducing the relapse risk due to longer drug half-life elimination10. In addition, less frequent therapy administrations (three-monthly) result in a higher quality of life than those with more frequent administrations (one-monthly and bi-weekly)11. A recent analysis has shown that therapies with extended coverage and longer administration interval reduce the risk of relapse after discontinuation10. The assumption made in the base case can be considered conservative as it shows that three-monthly antipsychotic therapy has the same continuation rate as the one-monthly therapy after 90 days of treatment but higher time on treatment due to the fact that patients could only discontinue the three-monthly therapy after 90 days of administration. The additional scenario is likely based on a realistic assumption, since the continuation rate after the first administration interval is similar to that of PP1M. The European Medicine Agency has recently granted the marketing authorization to paliperidone palmitate three-monthly formulation (Trevicta®) which is the first therapy to be administered only four times a year in schizophrenia for patients who have been stable on treatment with PP1M12. LIMITATIONS There is more than one reason for patients to discontinue their treatments. Unfortunately, those reasons were not identified in the previous analyses that were conducted in Belgium and the Netherlands6,7, thus it was assumed in the simulation of 90-day therapy interval that factors affecting treatment discontinuation of the threemonthly therapy are similar to those of the one-monthly therapy. This analysis was based on conservative assumptions, therefore further investigation on the impact of administration interval on time on treatment in the real world is needed. CONCLUSIONS Figure 2. Time on medication in Belgium as described in the additional scenario Therapies with a longer administration interval can prolong time on treatment and decrease the relapse risk. Therapies with less frequent administration allow physicians to focus on other elements of patient care, and patients to focus on aspects in life that means most to them. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Poster presented at 19th ISPOR Annual European Congress Vienna 2016 Hert MD et al. CNS Drugs. 2015;29(8):637–58. Leucht et al. Schizophrenia Research. 2012;136. Robinson et al. Arch Gen Psychiatry Archives of General Psychiatry. 1999Jan;56(3):241 Birchwood et al. International Clinical Psychopharmacology. 1998;13 Munro et al. The Psychiatrist. 2011;35(3):95–100. Denee et al. Treatment Continuation and Treatment Characteristics of Four Long Acting Antipsychotic Medications in The Netherlands. Poster presented at ISPOR Annual European Congress, Milan, Italy; 2015. Sermon et al. Treatment Continuation and Treatment Characteristics of 3 Long Acting Antipsychotic Medications (Paliperidone Palmitate, Risperidone Microspheres And Haloperidol Decanoate) In Belgium. Poster presented at ISPOR Annual European Congress, Amsterdam, The Netherlands; 2014. Mehnert A, Diels J. Impact of Administration Interval on Treatment Retention with Long-acting Antipsychotics in Schizophrenia. Poster presented at the Tenth Workshop on Cost and Assessment in Psychiatry. Venice, Italy; 2011. Sonnenberg et al. Medical Decision Making. 1993Jan;13(4):322–38 Kim et al. Time to Schizophrenia Relapse in Relapse-prevention Studies of Antipsychotics Developed for Administration Daily, Once Monthly, and Once Every 3 Months. Poster presented at the 15th International Congress on Schizophrenia Research, Colorado Springs, USA; 2015. Osborne et al. Health and Quality of Life Outcomes Health Qual Life Outcomes. 2012;10(1):35. European Medicines Agency - Find medicine - Trevicta (previously Paliperidone Janssen) [Internet]. Ema.europa.eu. 2016 [cited 26 August 2016]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004066/human_med_001829.jsp&mid=WC0b01ac058001d124 PMH43