Challenges facing drug utilization research in the Latin American region.

PURPOSE: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region. METHODS: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region. RESULTS: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions. CONCLUSIONS: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system.

Stimulant use following the publicity of cardiovascular safety and the introduction of patient medication guides.

PURPOSE: To explore changes in stimulant utilization and pre-treatment electrocardiography (ECG) screening in response to cardiovascular (CV) safety concerns. METHODS: Two source populations were established from Florida Medicaid Fee-for-service beneficiaries between 2001 and 2008: approximately 44 571 newly diagnosed attention deficit/hyperactivity disorder patients and 33 000 new stimulant users. Time-series design and Joinpoint analysis were used to describe monthly trend changes in stimulant initiation, persistence, dosing, and pre-treatment ECG screening. RESULTS: Initial and maintenance daily dose declined 6 mg (95% confidence interval [CI] -14 to -1.9) methylphenidate (MPH) equivalent dose from a steady 27 mg after Canada withdrew Adderall XR in February 2005; the trend rebounded to a daily dose of 23 mg, after the remarketing of Adderall XR and a debate in the US over issuing a boxed warning on stimulant CV safety in early 2006. Monthly initiation increased 3.9% (CI -1.0 to 9.1) after the boxed warning debate to 54 per 100 patients per month (CI 44 to 68), but declined 2.4% (CI -3.6 to -1.2) after requirement of medication guides in February 2007. Monthly ECG screening increased 3.2% (CI 2.3 to 4.2) after Adderall XR withdrawal and further increased 13% (CI 4 to 23) after the American Heart Association recommended pre-treatment ECG screening to 40 per 100 patients per month (CI 17 to 48). CONCLUSIONS: The first signal of stimulant CV safety concerns was followed by varying responses depending on the outcome measure used, suggesting that patients and physicians responded at different times after the publicity of safety concerns. Clinical consequences of the changes are uncertain. Copyright © 2015 John Wiley & Sons, Ltd.

Application of multicategory exposure marginal structural models to investigate the association between long-acting beta-agonists and prescribing of oral corticosteroids for asthma exacerbations in the Clinical Practice Research Datalink.

OBJECTIVE: To examine the comparative effectiveness of inhaled long-acting beta-agonist (LABA), inhaled corticosteroid (ICS), and ICS/LABA combinations. METHODS: We used a retrospective cohort design of patients older than 12 years with asthma diagnosis in the Clinical Practice Research Datalink to evaluate asthma-related morbidity measured by oral corticosteroid (OCS) initiation within 12 months of initiating LABAs, ICSs, or ICSs/LABAs. Asthma severity 12 months before drug initiation (use of OCSs, asthma-related hospital or emergency department visits, and number of short-acting beta-agonist prescriptions) and during follow-up (short-acting beta-agonist prescriptions and total number of asthma drug classes) was adjusted as a time-varying variable via marginal structural models. RESULTS: A total of 51,103 patients with asthma were followed for 12 months after receiving first prescription for study drugs from 1993 to 2010. About 92% initiated ICSs, 1% initiated LABAs, and 7% initiated ICSs/LABAs. Compared with ICSs, LABAs were associated with a 10% increased risk of asthma exacerbations requiring short courses of OCSs (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.07-1.18). ICS/LABA initiators were 62% less likely than ICS initiators (HR 0.38; 95% CI 0.12-0.66) and 50% less likely than LABA initiators to receive OCS prescriptions for asthma exacerbations (HR 0.50; 95% CI 0.14-0.78). CONCLUSIONS: In concordance with current asthma management guidelines, inhaled LABAs should not be prescribed as monotherapy to patients with asthma. The findings suggest the presence of time-dependent confounding by asthma severity, which was accounted for by the marginal structural model.

Pediatric exclusivity: evolving legislation and novel complexities within pediatric therapeutic development.

OBJECTIVE: To review the successes and omissions of the Food and Drug Administration (FDA) pediatric exclusivity incentive. DATA SOURCES: Pediatric drug development receives less attention and funding than drug development targeting adults resulting in fewer appropriately labeled pediatric drugs. Newly introduced legislation aims to correct this deficit using market exclusivity incentives. Under the Food and Drug Administration Modernization Act (FDAMA, 1997), the FDA established the exclusivity principle. This legislation was renewed and amended in 2007 under Food and Drug Administration Amendments Act (FDAAA) allowing drug companies to receive a 6-month patent extension for initiating clinical investigation in pediatric populations. Fostering improved knowledge in pediatric indications and dosing is the motivating force behind this program. STUDY SELECTION AND DATA EXTRACTION: We examined drugs granted exclusivity through FDA published database as well as relevant drug labeling and postmarket safety studies. Our examination shows that studies conducted in support of patent protection are often not designed to meet current pediatric needs. CONCLUSION: Amendments to FDAAA are needed to ensure that studies approved for exclusivity strive to meet the following requirements: relevant pediatric clinical indication ; disease addressed should represent a significant disease burden to the appropriate population; important age ranges should be covered; studies should not be allowed when a safety signal is identified prior to initiation of the study; and trials where endpoints are successfully achieved providing considerable contribution to pediatric dosing knowledge or result in labeling changes may gain an additional incentive.

Evaluating the impact of database heterogeneity on observational study results.

Clinical studies that use observational databases to evaluate the effects of medical products have become commonplace. Such studies begin by selecting a particular database, a decision that published papers invariably report but do not discuss. Studies of the same issue in different databases, however, can and do generate different results, sometimes with strikingly different clinical implications. In this paper, we systematically study heterogeneity among databases, holding other study methods constant, by exploring relative risk estimates for 53 drug-outcome pairs and 2 widely used study designs (cohort studies and self-controlled case series) across 10 observational databases. When holding the study design constant, our analysis shows that estimated relative risks range from a statistically significant decreased risk to a statistically significant increased risk in 11 of 53 (21%) of drug-outcome pairs that use a cohort design and 19 of 53 (36%) of drug-outcome pairs that use a self-controlled case series design. This exceeds the proportion of pairs that were consistent across databases in both direction and statistical significance, which was 9 of 53 (17%) for cohort studies and 5 of 53 (9%) for self-controlled case series. Our findings show that clinical studies that use observational databases can be sensitive to the choice of database. More attention is needed to consider how the choice of data source may be affecting results.

Male breast cancer and 5α-reductase inhibitors finasteride and dutasteride.

PURPOSE: We examined the association between 5α-reductase inhibitors and male breast cancer. MATERIALS AND METHODS: Study participants were men 40 to 85 years old, with prescription and medical coverage, enrolled in the United States IMS LifeLink™ Health Plan claims database between 2001 and 2009. Cases required a primary breast cancer diagnosis (ICD-9-CM 175.x) on 2 different dates and a procedural code for mastectomy or lumpectomy/partial mastectomy with evidence of continuous care (radiation/chemotherapy or diagnoses in 2 or more months). Eligible controls were within 5 years in age and had duration of prior health care enrollment within 6 weeks. Risk set sampling selected 20 controls per case. We assessed the rate ratio for male breast cancer with 5α-reductase inhibitor exposure using conditional logistic regression. Analyses were stratified by duration of health care enrollment before diagnosis (1 year or more, 2 years or more and 3 years or more), each incremental 180 and 365 days of cumulative 5α-reductase inhibitor exposure, and period specific time frames before diagnosis (years 1, 2 and 3). RESULTS: We identified 339 breast cancer cases matched to 6,780 controls. No statistically significant associations were observed between 5α-reductase inhibitors and breast cancer regardless of exposure assessment before the index date (1 year or more-RR 0.70, 95% CI 0.34-1.45; 2 years or more-RR 0.59, 95% CI 0.24-1.48; or 3 years or more-RR 0.75, 95% CI 0.27-2.10). Each subsequent 180 days (RR 1.02, 95% CI 0.67-1.53) and 365 days (RR 1.03, 95% CI 0.45-2.37) of cumulative 5α-reductase inhibitor therapy and period specific rate ratios also showed null associations. CONCLUSIONS: The lack of an association in our study suggests that the development of breast cancer should not influence the prescribing of 5α-reductase inhibitor therapy.

Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis.

BACKGROUND: There is an increased risk of venous thromboembolism among women taking oral contraceptives. However, whether there is an additional risk among women with polycystic ovary syndrome (PCOS) is unknown. METHODS: We developed a population-based cohort from the IMS LifeLink Health Plan Claims Database, which includes managed care organizations in the United States. Women aged 18-46 years taking combined oral contraceptives and who had a claim for PCOS (n = 43 506) were matched, based on a propensity score, to control women (n = 43 506) taking oral contraceptives. Venous thromboembolism was defined using administrative coding and use of anticoagulation. We used Cox proportional hazards models to assess the relative risk (RR) of venous thromboembolism among users of combined oral contraceptives with and without PCOS. RESULTS: The incidence of venous thromboembolism among women with PCOS was 23.7/10 000 person-years, while that for matched controls was 10.9/10 000 person-years. Women with PCOS taking combined oral contraceptives had an RR for venous thromboembolism of 2.14 (95% confidence interval [CI] 1.41-3.24) compared with other contraceptive users. The incidence of venous thromboembolism was 6.3/10 000 person-years among women with PCOS not taking oral contraceptives; the incidence was 4.1/10 000 person-years among matched controls. The RR of venous thromboembolism among women with PCOS not taking oral contraceptives was 1.55 (95% CI 1.10-2.19). INTERPRETATION: We found a 2-fold increased risk of venous thromboembolism among women with PCOS who were taking combined oral contraceptives and a 1.5-fold increased risk among women with PCOS not taking oral contraceptives. Physicians should consider the increased risk of venous thromboembolism when prescribing contraceptive therapy to women with PCOS.

Risk of acute kidney injury associated with the use of fluoroquinolones.

BACKGROUND: Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers. METHODS: We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis. RESULTS: We identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute increase in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin-angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithromycin was not associated with acute kidney injury. INTERPRETATION: We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin-angiotensin-system blockers.

Polycystic ovary syndrome and combined oral contraceptive use: a comparison of clinical practice in the United States to treatment guidelines.

The October 2010 ESHRE/ASRM polycystic ovary syndrome (PCOS) workshop concluded: (1) all combined oral contraceptives (COC) appear to have equal efficacy for PCOS, (2) addition of antiandrogens (spironolactone) to COCs has little treatment benefit and (3) metformin does not improve the live-birth rate and should only be used with impaired glucose tolerance. We compared these guidelines to current practice in the United States IMS claims-database. Time-series analyses were conducted by calendar-year in women with PCOS to evaluate prescribing preferences for COCs, concomitant use of spironolactone, and utilization of metformin. Trends were analyzed with linear regression. Our cohort included 1.6 million women taking COCs, 46 780 with a PCOS claim. Drospirenone utilization increased by 1.52% (SE:0.48%, p = 0.007) per-year more in women with PCOS (4.16%, SE:0.45%, p < 0.001) than in women without PCOS (2.64%, SE:0.17%, p < 0.001)). Concomitant use of drospirenone and spironolactone was common (14.26%) and increased by 0.75% (SE:0.15%, p = 0.002) per-year. Although plasma glucose tests were unavailable, women with PCOS were more likely to take metformin than have a diabetes claim (45.8% versus 15.2%, p < 0.001), indicating some women likely receive metformin solely for PCOS. Our data suggests further attention is needed to medication management of PCOS to bridge the gap between guidelines and practice.

Empirical assessment of methods for risk identification in healthcare data: results from the experiments of the Observational Medical Outcomes Partnership.

BACKGROUND: Expanded availability of observational healthcare data (both administrative claims and electronic health records) has prompted the development of statistical methods for identifying adverse events associated with medical products, but the operating characteristics of these methods when applied to the real-world data are unknown. METHODS: We studied the performance of eight analytic methods for estimating of the strength of association-relative risk (RR) and associated standard error of 53 drug-adverse event outcome pairs, both positive and negative controls. The methods were applied to a network of ten observational healthcare databases, comprising over 130 million lives. Performance measures included sensitivity, specificity, and positive predictive value of methods at RR thresholds achieving statistical significance of p < 0.05 or p < 0.001 and with absolute threshold RR > 1.5, as well as threshold-free measures such as area under receiver operating characteristic curve (AUC). RESULTS: Although no specific method demonstrated superior performance, the aggregate results provide a benchmark and baseline expectation for risk identification method performance. At traditional levels of statistical significance (RR > 1, p < 0.05), all methods have a false positive rate >18%, with positive predictive value <38%. The best predictive model, high-dimensional propensity score, achieved an AUC = 0.77. At 50% sensitivity, false positive rate ranged from 16% to 30%. At 10% false positive rate, sensitivity of the methods ranged from 9% to 33%. CONCLUSIONS: Systematic processes for risk identification can provide useful information to supplement an overall safety assessment, but assessment of methods performance suggests a substantial chance of identifying false positive associations.

Utilizing Medicare claims data for real­time drug safety evaluations:is it feasible?

PURPOSE: The Centers for Medicare & Medicaid Services claims comprise an administrative database of beneficiary-specific clinical information. This study evaluates the impacts of (i) claim information updates (claims adjudication) and (ii) delay in claim processing (claims delay) on real-time evaluation of health service and drug safety signals using the Medicare database. METHODS: Using Medicare claims data accumulated through May 2009 on health services rendered in 2006 and drugs dispensed in 2007, this study measures the frequency with which clinical information changes in the database as a result of (i) claims adjudication and (ii) claims delay. RESULTS: Over 85% of health services claims were processed within 8 weeks after the date of service, and 72% of drug claims were processed within 3 months after the dispense date. Clinical information changed for no more than 3% of unique claim groups in inpatient hospital, outpatient institutional, physician's office, and prescription drug Medicare claim settings. CONCLUSIONS: Claims delay is consistent across time and is minimal. Claims adjudication does not substantially impact the content of clinical information in the Medicare claims database. Therefore, the Medicare claims database provides consistent information regarding health services and prescription drugs in a manner that is prompt enough to facilitate medical product safety evaluations in real time.

Advancing the science for active surveillance: rationale and design for the Observational Medical Outcomes Partnership.

The U.S. Food and Drug Administration (FDA) Amendments Act of 2007 mandated that the FDA develop a system for using automated health care data to identify risks of marketed drugs and other medical products. The Observational Medical Outcomes Partnership is a public-private partnership among the FDA, academia, data owners, and the pharmaceutical industry that is responding to the need to advance the science of active medical product safety surveillance by using existing observational databases. The Observational Medical Outcomes Partnership's transparent, open innovation approach is designed to systematically and empirically study critical governance, data resource, and methodological issues and their interrelationships in establishing a viable national program of active drug safety surveillance by using observational data. This article describes the governance structure, data-access model, methods-testing approach, and technology development of this effort, as well as the work that has been initiated.

US national trends in bariatric surgery: A decade of study.

BACKGROUND: Since the 1990s, the number of bariatric surgeries has dramatically increased, including the number of bariatric centers in the United States; no recent studies have yet assessed trends of bariatric surgery. This study aims to assess the trends of bariatric surgery and the change in utilization by the type of surgery, from 2006 to 2015, using real-world data. METHODS: A cross-sectional analysis of MarketScan databases of privately insured beneficiaries aged equal to or more than 18 years, to assess the annual incidence rate of bariatric surgery type of surgery from 2006 to 2015. Linear regression analysis was used to assess the significance of bariatric surgery changes over time. RESULTS: A gradual increase in overall bariatric surgery was observed from 43.5 per 100,000 in 2006 to 70.6 per 100,000 in 2009. This increasing trend plateaued from 2010 to 2015. Among all bariatric surgeries performed, the sleeve gastrectomy showed a significant increase from (n = 596) 11% in 2006 to (n = 15,425) 70% in 2015 (P < .001), whereas there was a decrease in Roux-en-Y from (n = 10,129) 45% in 2010 to (n = 5074) 24% in 2015 (P < .001). CONCLUSION: Utilization of bariatric surgery showed a gradual increase in the first 5 years, with steady rates in the last 5 years of the study period. Sleeve gastrectomy and Roux-en-Y remain the most performed bariatric procedures. Laparoscopic surgery continues to dominate bariatric surgery compared with open surgery.

Metabolic syndrome and metabolically healthy status in adults with overweight or obesity, expressing no desire to lose weight.

AIM: To examine the prevalence of metabolic syndrome (MetS) and metabolically healthy status (MHS) in adults with excess weight, who express no desire to lose weight (DLW). METHODS: We used the National Health and Nutrition Examination Survey (2011-2016) to conduct a cross-sectional analysis of 4509 adults with excess weight. The prevalence of MetS and MHS was estimated by a DLW status. The prevalence ratios (PRs) were estimated, adjusting for demographic characteristics, to compare the prevalence of MetS and MHS between those with and without a DLW. RESULTS: Among adults who were overweight, the crude prevalence of MetS was 28.9% (95% CI 23.7, 34.1) in the no-DLW group and 36.0% (95% CI 31.9, 40.0) in the DLW group (adjusted PR 0.88; 95% CI 0.70, 1.11). Among adults with obesity, the crude prevalence of MetS was 60.0% (95% CI 52.3, 67.6) in the no-DLW group and 63.2% (95% CI 60.0, 66.4) in the DLW group (adjusted PR 1.00; 95% CI 0.88, 1.14). Among adults who were overweight, the prevalence of MHS was 17.5% (95% CI 13.4, 22.2) in the no-DLW group, and 9.5% (95% CI 7.6, 11.6) in the DLW group (adjusted PR 1.27; 95% CI 0.96, 1.69). Nearly all adults with obesity had at least one component of MetS regardless of DSW status. CONCLUSIONS: One in four overweight adults and three in five obese adults without a DLW had MetS in the U.S. A majority of adults who were overweight or obese without a DSW had at least one component of MetS.

The cost of health care for children and adults with sickle cell disease.

Although sickle cell disease (SCD) is marked by high utilization of medical resources, the full cost of care for patients with SCD, including care not directly related to SCD, is unknown. The purpose of this study was to estimate the total cost of medical care for a population of children and adults with SCD. We used data from individuals diagnosed with SCD enrolled in the Florida Medicaid program during 2001-2005 to estimate total, SCD-related, and non-SCD-related cost per patient-month based on patient age at the time of health care use. Across the 4,294 patient samples, total health care costs generally rose with age, from $892 to $2,562 per patient-month in the 0-9- and 50-64-year age groups, respectively. Average cost per patient-month was $1,389. Overall, 51.8% of care was directly related to SCD, the majority of which (80.5%) was associated with inpatient hospitalizations. Notably, non-SCD-related costs were substantially higher than those reported for the general US population. These results suggest a discounted (3% discount rate) lifetime cost of care averaging $460,151 per patient with SCD. Interventions designed to prevent SCD complications and avoid hospitalizations may reduce the significant economic burden of the disease.

Development and evaluation of a patient empowerment video to promote hydroxyurea adoption in sickle cell disease.

BACKGROUND: For the last decade, compelling evidence on hydroxyurea (HU) efficacy in certain adult patients with sickle cell disease (SCD) has supported recommendations for use of this drug to decrease morbidity and medical costs. Despite these benefits, HU therapy is underused in patients meeting treatment criteria. The purpose of this study was to develop and evaluate an educational video to empower patients and their families to initiate a conversation with their physicians on the benefits and risks of HU, encouraging a shared decision-making process. METHODS: Patients with SCD and physicians with prominence in the sickle cell community were selected to participate in the video based on their communication skills. They were encouraged to answer interview questions on camera with language that could be easily understood by all patients. Two focus groups participated in the development process verifying the messages in the video were clear and easy to understand. A pre- and postdesign survey of patients was performed to assess patient acceptability and utility of the video. RESULTS: A 15-minute educational video was produced and modified from input of the focus groups. Impact of the refined educational video was evaluated with a patient survey. Patients expressed a strong desire after viewing the video to learn about potential benefits of HU. Furthermore, the video was useful in heightening the intent of patients to ask their health care providers about HU therapy.

Decline in dopamine agonists prescribing and characteristics of drugs prescribed during ambulatory office visits for restless legs syndrome: the National Ambulatory Medical Care Survey 2007-2015.

OBJECTIVE: To examine prescribing of drugs treating or exacerbating restless legs syndrome (RLS) during U.S. physician office visits for RLS for the years 2007-2015; and to assess potential prescribing predictors of these drugs. METHODS: Using the National Ambulatory Medical Care Survey data, we conducted a retrospective cross-sectional study. We calculated weighted percentages of RLS-related office visits associated with RLS treatment drugs (alpha-2-delta ligands, dopamine agonists, and other drugs used for RLS) and exacerbating drugs. Using logistic regression, we examined the adjusted association between potential predictors and prescribing of major RLS treatment (dopamine agonists and alpha-2-delta ligands) and exacerbating drugs. RESULTS: A total of 456 RLS-related office visits were included for analysis, representing approximately 9.9 million visits. The weighted percentages of visits with dopamine agonists (excluding levodopa) decreased from 50% to 22% (RR 0.44; 95% CI 0.26, 0.77). A visit to a neurologist was associated with a 76% increase in prescribing of the major RLS treatment drugs compared with a visit to a family/general or internal medicine physician (RR 1.76; 95% CI 1.29, 2.42). RLS exacerbating drugs were listed in 28% (95% CI 21-36) of RLS-related visits, mostly for antidepressants (83%). Younger age groups (18-44 and 45-64) were predictors of RLS exacerbating drug prescribing, compared with the older age group (RR 2.46; RR 2.00, respectively). CONCLUSION: Prescribing of dopamine agonists during RLS-related visits decreased during 2007-2015, but prescribing of RLS exacerbating drugs remained high. More investigation is necessary concerning whether clinicians assess the appropriateness of RLS exacerbating drugs for RLS patients before newly prescribing or continuing those drugs. Also, future research would need to investigate what factors contribute to the difference in the RLS treatment prescribing patterns between neurologists and family/general or internal medicine physicians.

Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy.

BACKGROUND AND AIMS: Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS: Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS: In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% in UC cohort). In the first year, adalimumab had the highest persistence and lowest switching rates for both CD (median survival time: 1.04 years) and UC (median survival time: 0.84 years). In subsequent years, infliximab users were more likely to persist in the use of biologic. Combination therapy with immunomodulators significantly decreased the risk of discontinuation, especially when immunomodulator therapy was started more than 30 days before the biologic (hazard ratio [HR], 0.22; CI, 0.16, 0.32). The major predictors for noncompliance included infection and hospitalization. CONCLUSION: Overall, the persistence profiles of biologics suggest a high rate of dissatisfaction or adverse disease outcomes resulting in discontinuation and switching to a different agent. Early initiation of immunomodulators will substantially increase the persistence of biologic treatment.