Comparing Efficacy of Guselkumab versus Ustekinumab in Patients with Psoriatic Arthritis: An Adjusted Comparison Using Individual Patient Data from the DISCOVER and PSUMMIT Trials.

INTRODUCTION: Two biologic therapies for psoriatic arthritis (PsA), guselkumab and ustekinumab, have demonstrated superior efficacy versus placebo in clinical trials. However, no head-to-head studies have been conducted comparing these two treatments for PsA. The objective was to indirectly compare guselkumab and ustekinumab on joint and skin efficacy up to week 52, using pooled individual patient-level data (IPD) from PsA trials. METHODS: IPD, including baseline characteristics, American College of Rheumatology (ACR) scores and Psoriasis Area Severity Index (PASI) response from guselkumab (DISCOVER-1 and -2) and ustekinumab (PSUMMIT 1 and 2) trials were pooled. Differences in patient characteristics across trials were adjusted using multivariate logistic regression. Odds ratios (OR) were used to derive absolute response probabilities in the guselkumab trial population and were presented with 95% confidence intervals. RESULTS: Most baseline characteristics for guselkumab-treated patients (100 mg every 8 weeks [Q8W]; 100 mg every 4 weeks [Q4W]) were comparable to ustekinumab-treated patients (45/90 mg). In biologic-naïve patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 1.97; 1.37, 2.84; Q4W: 2.04; 1.40, 2.96) and PASI 90 (Q8W: 2.33; 1.52, 3.56; Q4W: 2.57; 1.67, 3.97) versus ustekinumab from week 16 onwards. In biologic-experienced patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 2.57; 1.11, 5.93; Q4W: 2.63; 1.12, 6.17) versus ustekinumab from week 24 onwards; for PASI 90, both guselkumab doses were superior to ustekinumab at week 16 and 52 (Q8W: 3.96; 1.39, 11.27; Q4W: 13.10; 4.18, 41.04). Guselkumab efficacy was similar and robust across primary, scenario, and sensitivity analyses. CONCLUSIONS: IPD analysis demonstrated that both guselkumab doses were superior to ustekinumab for ACR 20 from weeks 16 (biologic-naïve) and 24 (biologic-experienced) onwards, and for PASI 90 at weeks 16 and 52 for both subgroups.

Matching-adjusted indirect comparison (MAIC) results confirmed by head-to-head trials: a case study in psoriasis.

BACKGROUND: Head-to-head comparisons through randomized controlled trials (RCTs) provide high-quality evidence to inform healthcare decisions. In their absence, indirect comparisons are often performed; however, evidence is limited on how valid matching-adjusted indirect comparison (MAIC)-based comparative efficacy estimates are vs. RCT-based estimates. OBJECTIVES: Compare MAIC and RCT results of guselkumab vs. secukinumab and ixekizumab to provide insight into the validity of results generated using MAIC methods. METHODS: Previously reported results from MAICs of guselkumab vs. secukinumab and ixekizumab were compared with results from ECLIPSE and IXORA-R RCTs based on risk differences between Psoriasis Area and Severity Index (PASI) 90 response rates. RESULTS: Risk difference (95% confidence interval) in PASI 90 response rates at week 48 for guselkumab vs. secukinumab was 14.4% (9.4%; 19.4%) in ECLIPSE and 9.4% (4.7%; 14.0%) in the MAIC. The risk difference at week 24 for guselkumab vs. ixekizumab was 0.0% (-5.4%; 5.4%) in IXORA-R and 0.7% (-5.1%; 6.4%) in the MAIC. CONCLUSIONS: Comparative efficacy results were consistent between MAICs and RCTs of guselkumab vs. secukinumab and ixekizumab. This analysis demonstrates that MAIC methods can provide valid relative treatment effect estimates when direct comparisons are lacking, particularly when trials with similar designs and patient populations inform the analysis.

Persistence With Biologic Treatments in Psoriasis: A Structured Literature Review of Studies Using Administrative Database and Clinical Registry Data.

BACKGROUND: Psoriasis is a chronic, autoimmune-mediated inflammatory disorder. Drug persistence is a composite measure of effectiveness, safety, and treatment satisfaction, often estimated using data from administrative databases and clinical registries. Persistence rates calculated from these two data sources appear to be systematically different. OBJECTIVE: Review and compare persistence rates of psoriasis-indicated biologics reported in registry and database studies. METHODS: A structured literature search of studies published during 2009-2019 was performed in PubMed and American Academy of Dermatology records to identify research describing persistence with biologic treatments in psoriasis patients. English language retrospective or prospective persistence studies based on database or registry data, and reporting on at least two psoriasis-indicated biologics, of which at least one was ustekinumab, secukinumab, ixekizumab or guselkumab, were included. Single-arm studies, randomized control trials, systematic literature reviews, and studies presenting stratified results only were excluded. RESULTS: A total of 37 studies (22 registry- and 15 database-derived) comprising 76,000 patients were included. On average, drug persistence collected from registry studies was 18% higher than database studies. CONCLUSION: The findings of this study may be used by practitioners to make meaningful comparisons between persistence data derived from registries and databases, and thereby improve clinical decision making. J Drugs Dermatol. 2022;21(8):881-889. doi:10.36849/JDD.6789R1.

Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis.

OBJECTIVE: The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA). METHODS: A systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs). RESULTS: Twenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks. CONCLUSIONS: In this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.

Importance of assessing and adjusting for cross-study heterogeneity in network meta-analysis: a case study of psoriasis.

AIM: The importance of adjusting for cross-study heterogeneity when conducting network meta-analyses (NMAs) was demonstrated using a case study of biologic therapies for moderate-to-severe plaque psoriasis. METHODS: Bayesian NMAs were conducted for Psoriasis Area and Severity Index 90 response. Several covariates were considered to account for cross-trial differences: baseline risk (i.e., placebo response), prior biologic use, body weight, psoriasis duration, age, race and baseline Psoriasis Area and Severity Index score. Model fit was evaluated. RESULTS: The baseline risk-adjusted NMA, which adjusts for multiple observed and unobserved effect modifiers, was associated with the best model fit. Lack of adjustment for cross-trial differences led to different clinical interpretations of findings. CONCLUSION: Failure to adjust for cross-trial differences in NMA can have important implications for clinical interpretations when studying the comparative efficacy of healthcare interventions.

Relation Between Different Measures of Glycemic Exposure and Microvascular and Macrovascular Complications in Patients with Type 2 Diabetes Mellitus: An Observational Cohort Study.

INTRODUCTION: This retrospective cohort study investigated the relation between different measures of glycemic exposure and micro- and macrovascular complications among patients with type 2 diabetes. METHODS: The analysis included patients receiving oral antihyperglycemic agents between 1 January 2006 and 31 December 2014 from the General Practitioner Database from the PHARMO Database Network. All recorded HbA1c levels during follow-up were used to express glycemic exposure in four ways: index HbA1c, time-dependent HbA1c, exponential moving average (EMA) and glycemic burden. Association between glycemic exposure and micro-/macrovascular complications was analyzed by estimating hazard ratios and 95% confidence intervals using an adjusted (time-dependent) Cox proportional hazards model. RESULTS: The analysis included 32,725 patients (median age, 65 years; 47% female). Median follow-up was 5.4 years; median number of HbA1c measurements per patient was 18.0. From all measures, HbA1c at index showed the weakest relation between all micro-/macrovascular complications, with coronary artery disease (CAD) having the highest HR (95% CI): 1.18 (1.04-1.34) for HbA1c ≥64 mmol/mol (8%). The time-dependent HbA1c model showed a significant association only for microvascular complications, with retinopathy having the highest HR (95% CI): 1.55 (1.40-1.73) for HbA1c ≥64 mmol/mol (8%). EMA-defined exposure showed similar findings, although the effect of retinopathy was more pronounced [HR (95% CI): 1.81 (1.63-2.02) for HbA1c ≥64 mmol/mol (8%)] and was also predictive for CAD [HR (95% CI): 1.29 (1.10-1.50) for HbA1c ≥64 mmol/mol (8%)]. A statistically significant relation with glycemic burden was found for all selected micro-/macrovascular complications, with retinopathy having the highest HR (95%): 2.60 (2.19-3.07) for glycemic burden years >3. CONCLUSION: This study shows that greater and more prolonged exposure to hyperglycemia increases the risk of micro- and macrovascular complications. FUNDING: Janssen Pharmaceutica NV.

Evaluating the costs of glycemic response with canagliflozin versus dapagliflozin and empagliflozin as add-on to metformin in patients with type 2 diabetes mellitus in the United Arab Emirates.

OBJECTIVE: This study evaluates the cost of achieving glycemic control with three sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE). METHODS: A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26 ± 4 weeks in duration, published by 10 September 2014. A Bayesian network-meta analysis (NMA) compared HbA1c changes with canagliflozin 100 and 300 mg versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg. The cost associated with a 1% placebo-adjusted HbA1c reduction with each SGLT2 inhibitor as add-on to metformin was calculated based on NMA results and UAE drug costs. RESULTS: In the NMA, canagliflozin 100 and 300 mg were associated with HbA1c reductions (-0.67% and -0.79%) compared with dapagliflozin 10 mg (-0.41%) and empagliflozin 10 and 25 mg (-0.57% and -0.64%). Probabilities of canagliflozin 100 mg performing better were 79%, 60%, and 53% versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg, respectively; probabilities for canagliflozin 300 mg performing better were 88%, 72%, and 65%, respectively. The cost per 1%-point reduction in HbA1c was projected to be lower with canagliflozin 100 and 300 mg ($448 and $422) compared with dapagliflozin 10 mg ($785) and empagliflozin 10 and 25 mg ($527 and $563). CONCLUSIONS: Canagliflozin may provide a greater glycemic response at a lower effective cost than dapagliflozin or empagliflozin for patients with T2DM inadequately controlled with metformin from the payer perspective in the UAE.

Evaluation of economic effects of population ageing--methodology of estimating indirect costs.

Process of demographic ageing, especially in recent decades, is steadily growing in dynamics and importance due to increasing health-related needs and expectations with regard to a guarantee of social services. Elaboration of the most effective model of care, tailored to Polish conditions, requires an estimation of actual costs of this care, including indirect costs which are greatly related to informal care. The fact that the costs of informal care are omitted, results from a determined approach to analyses. It is discussed only from a perspective of budget for health and does not cover societal aspects. In such situation, however, the costs borne by a receiver of services are neglected. As a consequence, the costs of informal care are underestimated or often excluded from calculations, even if they include indirect costs. Comprehensive methodological approach for estimating the costs of informal care seems to be important for a properly conducted economic evaluation in health care sector.

Predictors of vocational status in schizophrenia patients--Results from the Polish nationwide survey.

BACKGROUND: Steady employment constitutes one of most important aspects of functional recovery in schizophrenia. Therefore, there is a need for understanding clinical and demographic factors predicting vocational status in schizophrenia. METHODS: Clinical and demographic data of 1,010 schizophrenia patients were gathered from public outpatient clinics. We compared patients who maintained employment between the diagnosis time point and the day of assessment, with the patients who were employed in the diagnosis time point but were unemployed on the day of assessment with respect to clinical and demographic variables. RESULTS: Lower educational attainment, lower-income region of residence, medical comorbidities (obesity, diabetes and hypertension), first hospitalization at inpatient unit in comparison with the day hospital, higher total number of hospitalizations and the number of inpatient hospitalizations were found to serve as predictors of unemployment throughout the course of schizophrenia. After application of Bonferroni correction and logistic binary regression analysis, lower educational attainment, higher number of inpatient hospitalizations and obesity predicted unemployment. CONCLUSION: Education, obesity and the number of inpatient hospitalizations seem to predict vocational outcome in schizophrenia. This study warrants further investigation of medical comorbidities in schizophrenia in terms of social consequences in order to indicate the direction of this relationship.

Costs of diabetes and its complications in Poland.

OBJECTIVE: Diabetes mellitus (DM) is a major health problem with severe complications and a significant impact on quality of life. It constitutes an enormous burden of disease due to high prevalence, severe co-morbidities and high costs for society. This study is the first comprehensive study on the direct and indirect costs of DM (type 1 and type 2) and associated complications in Poland. METHODS: In order to estimate the direct medical costs of DM and its complications, including the costs of medical consultation, hospitalisation, rehabilitation, drugs and medical equipment, data from the National Health Fund were used. Indirect costs on loss of productivity due to diabetes and its complications were based on data obtained from the ZUS (Social Insurance Institution) and from GUS (Poland's Central Statistical Office). Attributable risk methodology was used to assess the burden of DM complications. RESULTS: A continuous increase of the direct costs of diabetes has been observed since the year 2005. In the analysed time period (2005-2009) the direct costs of medical services for both types of DM doubled. DM is a cause of significant sickness absence and incapacity for work and therefore is associated with a growing productivity decline in Poland. The highest direct costs and indirect costs are associated with treatment of diabetes-related complications. Direct costs of hospital complication treatment were EUR 332 million, which exceeded by more than five times the direct costs of hospital treatment of diabetes per se, which in the same year amounted to EUR 58.5 million. The indirect costs of diabetes-related complications were higher by 41% compared with indirect costs related to DM itself. Total costs of health care services for DM and its complications amounted to EUR 654 million, which constitutes a 2.8% of total health care costs in Poland. Total DM cost in Poland in 2009 amounted EURO 1.5 billion. CONCLUSIONS: DM is causing a growing economic burden on the health care system and on Polish society in terms of health care and productivity losses. Most of the total cost of diabetes are indirect costs caused by productivity losses. Both direct and indirect costs are driven by the cost of diabetes complications.

Economic analysis of the implementation of guidelines for type 2 diabetes control developed by Diabetes Poland: what increase in costs is justified by clinical results?

INTRODUCTION: Diabetes Poland has recently published guidelines for the treatment of type 2 diabetes. Treatment according to these guidelines is more expensive and requires more involvement of the patient than is the case in current clinical practice. OBJECTIVES: The aim of the study was to assess to what extent the cost of type 2 diabetes treatment according to the Diabetes Poland guidelines may be increased when compared with the cost of the current treatment, so that the introduction of the guidelines remains cost-effective in the Polish setting. PATIENTS AND METHODS: Two hypothetical patients were defined, John and Peter, representing the population of newly diagnosed type 2 diabetic patients. The disease progression was simulated assuming that John is treated according to the current practice and Peter is treated to achieve and maintain the goals defined by Diabetes Poland. The simulation was performed using the CORE model, which has been constructed based on the published scientific evidence and includes more than a dozen of diabetes complications. The model has been widely validated by numerous studies and is broadly used; it enables a reliable estimation of costs and clinical effects associated with diabetes. The parameters of the model were adapted to the Polish conditions. The analysis was conducted in a life-long perspective, discounting of costs/effects was included, and the acceptability threshold was set at 25,511 EUR per quality-adjusted life-year (QALY). RESULTS: The quality-adjusted life expectancy of John will be 0.3 QALY lower than the life expectancy of Peter. The treatment of diabetic complications will be 400 EUR more expensive in the case of John compared with that of Peter. Assuming the willingness to pay at the level of 7500 EUR/QALY, the cost of diabetes treatment of Peter may be 250 EUR higher than that of John's treatment. For the threshold level of 15,000 EUR/QALY, the difference in cost may be 450 EUR, and for the threshold level of 25,000 EUR/QALY - 725 EUR per year. CONCLUSIONS: Treatment according to the guidelines of Diabetes Poland may be cost-effective provided that the additional costs associated with intensification of therapy will not exceed 725 EUR per year.