Background:Psoriatic arthritis (PsA) is a chronic, heterogeneous, immune-mediated seronegative arthritis characterized by joint inflammation in people with skin psoriasis (PsO). In recent years several effective biologic treatments such as tumour necrosis factor inhibitors (TNFi), interleukin (IL) 12 and 23 inhibitors (IL-12/23i), and IL 17 inhibitors (IL-17i) have been introduced for PsA. Discontinuation (non-persistence) of therapy is usually a consequence of lack of effect and intolerability.Objectives:Compare time to discontinuation of TNFi (adalimumab, ADA), IL-17i (secukinumab, SEC), and IL-12/23i (ustekinumab, UST) treatment exposures and the association with previous biologic treatment experience.Methods:Population-based national health data from the Swedish Patient Registry, Prescribed Drug Registry and Cause of Death Registry were linked at the patient level and used to identify treatment exposures in PsA patients initiating ADA, SEC, or UST between January 2008 and September 2018. Discontinuation was defined as a treatment switch to any other PsA-indicated biologic, or failure to re-dispense treatment within a grace period following end of drug supplied. The grace period, defined as the number of days between end of drug supply and re-dispensation during which a patient is considered to be on active treatment, was set dynamically to the number of days of drug supplied in the primary analysis. As a sensitivity analysis, a fixed 90-day grace period was used. Supply was calculated as total milligrams dispensed divided by maintenance dose posology, where the following assumptions were made due to the limitations of the administrative data used: UST patients’ weight corresponded to the amount of drug dispensed (both 45mg and 90mg dispensations last 84 days), SEC patients with prior TNFi experience consumed 300mg/28 days and all others consumed 150mg/28 days, and ADA patients consumed 40mg/14 days. Adjusted hazard ratios (HR) for time to discontinuation were calculated using a Cox proportional hazards model. Covariates for age, marital status, and previous biologic treatment experience were assessed at the initiation of treatment exposure, while comorbidity including skin PsO was assessed during the two years prior. Exposures without discontinuation events were censored at death or end of follow-up. The study was approved by the Stockholm Regional Ethical Review Board.Results:3,620 discontinuation events were observed in the main analysis across 4,649 treatment exposures (ADA: 3,255; SEC: 887; UST: 507) (Figure 1, unadjusted). 3,162 events were observed in the sensitivity analysis. Average age at treatment initiation was 50, 54% were female, 47% were biologic treatment naïve, and 39% had skin PsO. In the multivariate main analysis, UST exhibited lower discontinuation rates vs ADA (HR=0.56, 95% CI: 0.49-0.64) while there was no significant difference between SEC and ADA (HR=1.01, 95% CI: 0.88-1.15). In the multivariate sensitivity analysis, both UST (HR=0.81, 95% CI: 0.70-0.94) and SEC (HR=0.82, 95% CI: 0.70-0.95) were associated with significantly lower discontinuation rates ratio relative to ADA. Overall, patients with more biologic treatment experience were statistically significantly (p<0.05) associated with higher risk of treatment discontinuation.Figure 1.Unadjusted Kaplan-Meier curves of time to treatment discontinuation (main analysis, dynamic grace period)Conclusion:UST exhibits a favourable treatment persistency profile relative to ADA, regardless of the grace period definition. The relative risk of discontinuing SEC vs ADA is sensitive to the grace period. Treatment discontinuation was higher in treatment exposures with more biologic experience.Disclosure of Interests:Kirk Geale Consultant of: Quantify Research, Speakers bureau: Indirectly as a consultant, Ingrid Lindberg Consultant of: Quantify Research, Emma Paulsson Consultant of: Quantify Research, Christina Wennerström Employee of: Janssen-Cilag Sweden AB, Anna Tjärnlund Employee of: Janssen-Cilag Sweden AB, Virginia Taliadouros Shareholder of: JnJ, Employee of: Janssen Pharmaceuticals NV, Wim Noel Employee of: Janssen Pharmaceuticals NV, Dana Enkusson Employee of: Janssen-Cilag AB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB
INDONESIAN PATENT SYSTEM: AN OVERVIEW