Cohort Study on Drug Survival and Tolerability of Adalimumab Biosimilar Transitioning: Pharmaceutical Properties Do Matter.

Background:Drug survival is important for demonstrating the effectiveness of treatment in patients with axial spondyloarthritis (axSpA) in real life.Objectives:This study examines the drug survival rates and factors influencing discontinuation of...

Improving the Accuracy of Biologic Drug Survival Data: The Increasing Prevalence of Off-Label Dosing Must Be Considered when Reporting Drug Effectiveness and Safety

Background:Patient with rheumatoid arthritis (RA) who are obese often have a reduced response to DMARD treatment, including TNF inhibitors (TNFi). Considering the different mechanisms of action it is important to...

The data on long-term efficacy, safety and drug survival rates of conventional systemic therapeutics in pediatric psoriasis is lacking. The primary aim of this study is to investigate acitretin, methotrexate, cyclosporin efficacy, safety and drug survival rates in pediatric patients as well as predictors of drug survival. This is a multicenter study including 289 pediatric cases being treated with acitretin, methotrexate and cyclosporin in four academic referral centers. Efficacy, adverse events, reasons for discontinuation, 1, 2- and 3-year drug survival rates, and determinants of drug survival were analyzed. A 75% reduction of Psoriasis Area and Severity Index score or better response rate was obtained in 47.5%, 34.1% and 40% of the patients who were treated with acitretin, methotrexate and cyclosporin, respectively. One-year drug survival rates for acitretin, methotrexate and cyclosporin were 36.3%, 21.1% and 15.1%, respectively. The most significant determinant of drug survival, which diminished over time, was treatment response whereas arthritis, body mass index and sex had no influence. Although all three medications are effective and relatively safe in children, drug survival rates are low due to safety concerns at this age group. Effective disease control through their rational use can be expected to improve survival rates.

Long-term data of etanercept drug survival in patients with psoriasis in daily practice are scarce. The primary objective was to describe drug survival for etanercept in a long-term daily practice cohort of patients with psoriasis. The secondary objective was to identify determinants of drug survival for etanercept in general and separately for discontinuation due to adverse events or ineffectiveness of therapy. Data were extracted from a prospective daily practice cohort of patients treated with biologics for psoriasis. Drug survival was analysed by Kaplan-Meier survival curves and split for two reasons for discontinuation: adverse events and ineffectiveness. Determinants of drug survival were analysed using univariate Cox regression analysis and multivariate Cox regression analysis with backward selection. We included 193 patients (512 patient-years treated) with a maximum treatment duration of 7·5 years. The overall drug survival rates were 77%, 41% and 30% after 1, 4 and 7·5 years, respectively. The mean survival duration was 3·8 years (95% confidence interval 3·4-4·3). Reasons for discontinuation were ineffectiveness (33·7%), adverse events (11·9%), both ineffectiveness and adverse events (4·7%) or other reasons (e.g. pregnancy planned) (5·7%). Determinants related to longer general drug survival were male sex [hazard ratio (HR) 0·55], prior anti-tumour necrosis factor (TNF)-α use (HR 0·57) and lower etanercept dose (HR 0·65). Younger age (HR 0·83), lower body mass index (HR 0·63) and lower etanercept dose (HR 0·71) were related to a decreased risk of discontinuation due to side-effects. A lower mean weekly dose of etanercept (HR 0·63) was related to a decreased risk of discontinuation due to ineffectiveness of therapy. We present the longest analysis of drug survival for etanercept in psoriasis to date. Determinants of longer overall etanercept drug survival were male sex, prior anti-TNF therapy and lower etanercept dose. The determinants of longer drug survival depended on the reason for discontinuation of etanercept.

Long-term data of ciclosporin A (CsA) treatment in daily practice in patients with severe atopic dermatitis (AD) are lacking. To perform a detailed analysis of drug survival, which is the length of time a patient continues to take a drug, for CsA in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival. Data were extracted from a retrospective cohort of patients treated with CsA for AD. Drug survival was analysed using Kaplan-Meier survival curves. Determinants of drug survival were analysed using uni- and multivariate Cox regression analyses with backward selection. In total, 356 adult patients were analysed (386 patient-years). The overall drug survival rates were 34%, 18%, 12% and 4% after 1, 2, 3 and 6years, respectively. Reasons for discontinuation were controlled AD (26·4%), side-effects (22·2%), ineffectiveness (16·3%), side-effects plus ineffectiveness (6·2%) or other reasons (11·0%). Older age was associated with a decreased drug survival related to controlled AD [hazard ratio (HR) 0·91]. Older age was also associated with a decreased drug survival related to side-effects (HR 1·14). An intermediate-to-high starting dose (>3·5-5·0mgkg(-1) daily) was associated with an increased drug survival related to ineffectiveness (HR 0·63). This is the first study on drug survival for CsA treatment in AD. Older age was associated with decreased drug survival related to controlled AD and side-effects. An intermediate-to-high starting dose was associated with an increased drug survival related to ineffectiveness.

AB0264 Comparison of drug survival, safety and doses of etanercept, infliximab and adalimumab in rheumatoid arthritis patients: thirteen years canadian clinical practice experience.

ABSTRACTBackgroundThere is limited data on how drugs prescribed for functional bowel disorders are re‐prescribed in clinical practice. This study aimed to investigate drug survival rates of different irritable bowel syndrome (IBS) treatments among patients referred to a gastroenterologist.MethodsA retrospective observational study was conducted by reviewing medical charts of patients aged 18–50 years, diagnosed with IBS or an unspecified functional intestinal disorder between 2010 and 2018. Drug survival rates for various treatment categories were analyzed using Kaplan–Meier curves and log‐rank tests.ResultsA total of 1528 treatment attempts were recorded in 529 patients, with 883 classified as treatment‐naïve. Simethicones demonstrated significantly higher drug survival compared to bulking agents (p = 0.009). Tricyclic antidepressants (TCA), loperamide, and simethicones all showed superior survival rates compared to osmotic laxatives (p = 0.039, p = 0.025 and p = 0.003, respectively). Additionally, loperamide and simethicones had better survival rates than antispasmodics (p = 0.046 and p = 0.012, respectively). At 60 months, the cumulative drug survival rate was highest for TCA (11%), followed by loperamide (10%) and simethicones (7%), all significantly outperforming bulking agents (1%) (p = 0.002 for TCA vs. bulking agents, p = 0.002 for loperamide vs. bulking agents, and p = 0.006 for simethicones vs. bulking agents). For all treatment‐naïve attempts, the cumulative drug survival at 60 months was 6%.ConclusionsThe overall 60‐month drug survival for treatments prescribed in IBS is relatively low, suggesting that the effectiveness of current therapies remains limited. Among the medications studied, simethicone and TCAs demonstrated the best drug survival rates.

Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children. To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children. A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016. PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe). Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18). Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.

BackgroundBiologic drug survival is defined as the time from initiation of biologic therapy to discontinuation, which can be due to ineffectiveness, adverse events or other reasons. It is an important...

Drug persistence is a crucial aspect of treatment success in psoriasis. To record real-world evidence concerning drug survival of biologic agents used for psoriasis treatment and to detect associated modifying factors in Greece. This was a retrospective cohort study based on data extracted from the nationwide Greek prescription system. Included patients had psoriasis, with or without concomitant psoriatic arthritis (PsA), and had initiated biologics between 1 January 2016 and 31 December 2020. We included 8819 patients who received 13 359 treatment lines. Among them, 76.8% of patients were biologic naive and 16.5% were diagnosed with concomitant PsA. The overall median drug survival was 34.3 months [95% confidence interval (CI) 32.6-36.5]. Drug persistence at 12, 24, 36 and 48 months of follow-up was 71.9%, 57.7%, 49.0% and 43.7%, respectively. Patients receiving brodalumab had the highest drug survival rate in the first 2 years, while secukinumab had the highest rates beyond this period. Overall, drug survival rates were higher in the first treatment line (median 51.1 months, 95% CI 47.1 to not reached) than in the second line and onwards (median 21.7 months, 95% CI 20.0-23.5). Treatment line, PsA status, age and sex were found to significantly affect drug survival rates. Our findings confirm previous reports regarding the importance of efficient first-line biologics and the vulnerability of patients to coexistent PsA. The use of antibodies against interleukins confers high drug survival rates. These results will assist clinical management of patients with psoriasis in Greece.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that can have a negative impact on a patient's quality of life. Long-term effectiveness is required to manage the symptoms of AD (skin inflammation, eczematous lesions, and itching). Because some of the systemic immunosuppressants used to treat AD have been associated with serious adverse events (AEs), other safer, more effective options, including dupilumab, have been proven effective long-term for treatment of adult and adolescent patients with moderate-to-severe AD. The long-term safety and effectiveness of a drug are usually confirmed in real-world studies by evaluating its performance over time. Measures such as drug survival, drug retention, drug persistence, or retention rates reflect whether treatment may be considered as satisfactory by both patients and physicians, meeting key clinical needs. This review aimed to describe the survival, retention, or persistence of dupilumab therapy in adults and adolescents with moderate-to-severe AD by conducting a PubMed search in March 2023 and screening for relevant publications. Globally, real-world studies with dupilumab have regularly reported high drug survival rates after 1, 2, and 3years of observation, being consistently at 80-90%, with low rates of treatment discontinuation due to lack of efficacy or AEs. These findings are notably higher than 1- and 2-year drug survival rates of systemic immunosuppressants (including cyclosporine [37% and 20%, respectively] and methotrexate [41% and 33%, respectively]). Overall, real-world data on drug survival have confirmed that dupilumab provides long-term sustained efficacy and acceptable safety in patients with moderate-to-severe AD.

AB0228 LONG-TERM EFFECTIVENESS, DRUG SURVIVAL OF BIOLOGIC THERAPIES IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND SPONDYLOARTHRITIS AND PREDICTIVE FACTORS OF DRUG DISCONTINUATION DUE TO DISEASE REMISSION

AB0420 Drug survival on certolizumab and predictors thereof in patients with rheumatoid arthritis, psoriatic arthritis, and axial-spondyloarthritis from the apulian biopure registry