Background A substantial share of type 2 diabetes mellitus (T2DM) patients receive insulin. However, little is known about the real-world treatment patterns around insulin initiation. Methods This was a retrospective claims data analysis. T2DM patients who initiated an insulin therapy between 01/01/2013 and 31/12/2015 were identified in the German AOK PLUS dataset. For validation of results, additional data on a similar T2DM patient population were collected in a Germany-wide medical chart review. Results A total of 284,878 T2DM patients were identified. Of these, 27,340 (9.6%) initiated an insulin treatment during the inclusion period (mean age: 72.2 years; 51.4% female). Mean/median weight and BMI of patients with available clinical data was 85.8/84.0 kg (SD:18.9) and 30.6/29.8 kg/m 2 (SD:6.1), respectively at baseline. Mean/median HbA1c-value at baseline was 8.4/8.0% (SD: 1.8). Most commonly prescribed antidiabetic drugs (AD) within 6 months before insulin initiation were metformin (MET; 54.0%), DPP-4 inhibitors (DPP-4i; 37.6%), and sulfonylureas (SU; 29.5%). As high as 23.2% of the patients did not receive any AD prescription within 6 months before insulin initiation. A total of 10,953 of above 27,340 insulin starters (40.1%) initiated their insulin therapy without concomitant ADs (insulin monotherapy); 43% of these patients did not receive any AD before insulin initiation. Of the remaining 16,387 patients (59.9%), 4070 patients (14.9%) received MET only as concomitant AD, 6385 (23.4%) received MET plus at least one further AD, and 5932 (21.7%) received at least one further AD excluding MET. Throughout the first year of treatment, prescribed insulin dosage increased over time, resulting in approximately 43.3–77.9 IUs per observed patient day after 12 months of insulin treatment. Conclusions Characteristics of German T2DM patients initiating insulin deviate substantially from the average German population, especially in terms of weight. We identified an unexpectedly high number of patients without previous AD therapy receiving insulin monotherapy, which is not in line with the clinical guidelines.

Background Real-world data regarding response rates in ulcerative colitis treatment are rare, particularly for later lines of therapy. This study aimed to assess continuity of and changes to advanced therapies, as well as costs and specific indicators defining suboptimal therapy. Methods German claims data were retrospectively analyzed (January 2014 to June 2019). Patients with ulcerative colitis initiating an advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) were included. Inadequate response was indicated by therapy discontinuation, switch, escalation, augmentation, corticosteroid dependency, disease-related hospitalization, or surgery. Health care resource utilization (inpatient, outpatient, sick leaves, medication, aids, and remedies) and related costs were assessed from therapy initiation until discontinuation or loss to follow-up. Results Among 574 patients (median age, 39 years; female sex, 53.5%) who initiated advanced therapies, 458 (79.8%) received an antitumor necrosis factor therapy, 113 (19.7%) vedolizumab, and 3 (0.5%) tofacitinib. After 12 months, 75% had ≥1 indicator for suboptimal therapy. The median time to first indicated inadequate response was 4.8 months. Therapy discontinuation (38%), switching (26%), and prolonged use of steroids (36%) were common within the first year of treatment. In an unadjusted comparison, all-cause total costs per person-year were significantly higher in those who switched vs patients remaining on their therapy (€44,570 vs €36,807; P < .001). Conclusions Our study indicates a high prevalence of inadequate response to advanced therapies. Only 25% of patients showed adequate response within 12 months after therapy initiation. Frequent dose and treatment changes were observed. The economic impact of suboptimal therapy in ulcerative colitis is substantial, highlighting the ongoing need for improved treatment strategies.

Introduction Clinical guidelines recommend anticoagulation therapy for the treatment of cancer-associated venous thromboembolism (VTE), but little is known about preferences. Therefore, the objective of this discrete choice experiment (DCE) was to elucidate patient preferences regarding anticoagulation convenience attributes. Methods Adult patients with cancer-associated VTE who switched to direct oral anticoagulants were included in a single-arm study (COSIMO). Patients were asked to decide between hypothetical treatment options based on a combination of the following attributes: route of administration (injection/tablet), frequency of intake (once/twice daily), need for regular controls of the international normalized ratio (INR) at least every 3 to 4 weeks (yes/no), interactions with food/alcohol (yes/no), and distance to treating physician (1 vs. 20 km) as an additional neutral attribute. DCE data were collected by structured telephone interviews and analyzed based on a conditional logit regression. Results Overall, 163 patients (mean age 63.7 years, 49.1% female) were included. They strongly preferred oral administration compared with self-injections (importance of this attribute for overall treatment decisions: 73.8%), and a treatment without dietary restrictions (11.8%). Even if these attributes were less important (7.2% and 6.5%, respectively), patients indicated a preference for a shorter distance to the treating physician and once-daily dosing compared with twice-daily intake. “Need for regular controls of INR at least every 3 to 4 weeks” showed no significant impact on the treatment decision (0.7%). Conclusion This study showed that treatment-related decision making in cancer-associated VTE, assuming comparable effectiveness and safety of anticoagulant treatments, is predominantly driven by “route of administration,” with patients strongly preferring oral administration.

Background: This study describes real-world treatment-related outcomes and healthcare costs of German type 2 diabetes mellitus (T2D) patients who initiated insulin therapy. Methods: This retrospective analysis includes German claims data from 01/01/2012 until 31/12/2016. Identification of eligible patients took place between 01/01/2013 and 31/12/2015, allowing for at least 1 year of follow-up. Clinical outcomes, such as HbA1c values and body mass index, were observed in a subpopulation participating in a Disease Management Program. Healthcare expenditures were evaluated for the first year of therapy. Results: Overall, 27,340 insulin starters with T2D were observed (mean age: 72.2 years, female: 51.4%). Treatment-related outcomes were evaluated in a subsample of 12,034 patients. Patients who started insulin combined with other antidiabetic drugs (ADs) achieved their HbA1c goals more frequently than patients on insulin monotherapy (+10.7 percentage points [pp] vs. +21.1 pp for insulin plus metformin). All-cause costs were by far highest among patients with insulin monotherapy (€ 12,283 per patient-year) compared with patients receiving a combined AD regimen (€ 9,947-10,509 per patient-year). Conclusions: Changes in HbA1c values were not in favor of insulin monotherapy, compared to regimens including other ADs. It was also associated with higher costs, suggesting that insulin alone is a suboptimal treatment.

Introduction According to current guidelines, appropriate drug treatment is the backbone of the effective management of cardiovascular (CV) comorbidities in patients with type 2 diabetes mellitus (T2DM). The main objective of this study was to assess the degree of real-world adherence to these guideline recommendations and to identify whether poor guideline adherence is associated with worse clinical outcomes. Methods In this retrospective German claims data analysis (AOK PLUS dataset), patients with T2DM with an incident diagnosis (index date) of ischemic stroke, myocardial infarction, heart failure or coronary artery disease were observed for 12 months between 1 January 2014 and 31 December 2017. We assessed guideline adherence per observed CV disease combination at three levels: “green” if patients received prescriptions of all recommended medications with > 185 defined daily doses (DDDs) per observed patient-year; “yellow” if patients received at least two prescriptions of at least one of the recommended medications; and “red” if patients did not receive at least two prescriptions of at least one of the recommended medications. The impact of the assignment of a patient to one of these three levels on all-cause mortality and CV risk was analyzed based on multivariable Cox regression analyses and reported as adjusted hazard ratios (HRs). Results We identified 32,916 patients with T2DM with an incident CV comorbidity (mean age 75.0 years, 54.2% female, Charlson Comorbidity Index [CCI]: 5.5). Observed patients received at least 185 DDDs of the following medication classes in the 12 months before/after the index date: vitamin K antagonists (6%/6%); antiplatelet drugs (9%/27%); novel oral anticoagulants (3%/13%); diuretics (48%/54%); beta blockers (31%/35%); calcium-channel blockers (34%/32%); renin-angiotensin-aldosterone system inhibitors (69%/68%); and lipid-modifying agents (19%/37%). When post-index therapy was compared to guideline recommendations, the level of “guideline adherence” was classified as “green” for 14.4% of the patients, “yellow” for 75.2% and “red” for 10.5%. An assignment of “red” was associated with worse CV outcomes in all analyses. Regarding mortality, in addition to one additional year of age (hazard ratio [HR] 1.04), CCI (HR 1.17), use of insulins (HR 1.25), digitalis glycosides (HR 1.52) and diuretics (HR 1.32), non-adherence to guideline recommendations (“red”: HR 6.79; “yellow”: HR: 1.30) was a significant predictor for early death, while female gender (HR 0.79), the participation in a disease management program (HR 0.69) and the use of antidiabetics other than insulin (HR 0.74) were generally associated with a reduced risk. Conclusion Only a minority of patients with T2DM and an incident CV comorbidity receive a treatment fully adherent with guideline recommendations. This may contribute to high mortality rates in this population in clinical practice. Supplementary I...

Background Idiopathic pulmonary fibrosis (IPF) is a progressive form of fibrosing interstitial pneumonia with poor survival. This study provides insight into the epidemiology, cost, and disease course of IPF in Germany. Methods A cohort of incident patients with IPF (n = 1737) was identified from German claims data (2014–2019). Incidence and prevalence rates were calculated and adjusted for age differences compared with the overall German population. All-cause and IPF-related healthcare resource utilization as well as associated costs were evaluated per observed person-year (PY) following the initial IPF diagnosis. Finally, Kaplan–Meier analyses were performed to assess time from initial diagnosis to disease deterioration (using three proxy measures: non-elective hospitalization, IPF-related hospitalization, long-term oxygen therapy [LTOT]); antifibrotic therapy initiation; and all-cause death. Results The cumulative incidence of IPF was estimated at 10.7 per 100,000 individuals in 2016, 10.9 in 2017, 10.5 in 2018, and 9.6 in 2019. The point prevalence rates per 100,000 individuals for the respective years were 21.7, 23.5, 24.1, and 24.1. On average, ≥ 14 physician visits and nearly two hospitalizations per PY were observed after the initial IPF diagnosis. Of total all-cause direct costs (€15,721/PY), 55.7% (€8754/PY) were due to hospitalizations and 29.1% (€4572/PY) were due to medication. Medication accounted for 49.4% (€1470/PY) and hospitalizations for 34.8% (€1034/PY) of total IPF-related direct costs (€2973/PY). Within 2 years of the initial IPF diagnosis (23.6 months), 25% of patients died. Within 5 years of diagnosis, 53.1% of patients had initiated LTOT; only 11.6% were treated with antifibrotic agents. The median time from the initial diagnosis to the first non-elective hospitalization was 5.5 months. Conclusion The incidence and prevalence of IPF in Germany are at the higher end of the range reported in the literature. The main driver for all-cause cost was hospitalization. IPF-related costs were mainly driven by medication, with antifibrotic agents accounting for around one-third of the total medication costs even if not frequently prescribed. Most patients with IPF do not receive pharmacological treatment, highlighting the existing unmet medical need for effective and well-tolerated therapies.

Achieving good glycemic control in type 2 diabetes (T2DM) may require individualized pharmacological approaches. We aimed to compare direct healthcare costs in patients treated with empagliflozin (EMPA) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1-RA). Patients and Methods: This German claims data study included continuously insured persons with at least two outpatient diagnoses and/or one inpatient diagnosis of T2DM if they started EMPA, DPP-4i, or GLP-1-RA in 2015-2018. Healthcare costs were assessed from therapy initiation until the end of data availability, death, or therapy discontinuation and compared among propensity scorematched cohorts. Results: Of 24,465 patients included, 3285 received EMPA, 19,443 DPP-4i, and 1747 GLP-1-RA. Matched cohorts were balanced on baseline characteristics (EMPA versus DPP-4i: n 1 /n 2 = 3100/3100 and EMPA versus GLP-1-RA: n 3 /n 4 = 1346/1346). Mean total costs after start of DPP-4i were €7009 (95%-CI: 6573-7444) versus €4274 (3982-4566) for EMPA. Costs associated with GLP-1-RA treatment were also significantly higher compared with versus €4895 ). Conclusion: Although the individual clinical patient profile and physician assessment are paramount in treatment decisions, substantial differences in the economic impact of different antidiabetic therapies should be considered.

Background Advanced therapies used in moderate-to-severe Ulcerative Colitis (UC) may show a secondary loss of response (LOR) over time, requiring patients to undergo dose escalation or switching. Our study aimed to investigate the frequency of dose escalation in real-world practice and evaluated the associated cost. Methods Using German claims data (AOK PLUS) including prescription data, we identified UC patients by either at least two confirmed outpatient diagnoses or one primary inpatient diagnosis (ICD-10 K51). Analyzed patients initiated an advanced therapy (anti-TNF, vedolizumab, tofacitinib) between 01/01/2015-30/06/2019. Therapy escalation was defined as dose increase exceeding the recommended maintenance dose according to product labels by more than 150%. Time to first escalation was analyzed using a Kaplan-Meier estimation. The observation ended with the discontinuation of index therapy + 90 days, or loss to follow-up, whatever occurred first. End of therapy was determined in case of a supply gap of >60 days or switch of the advanced therapy. Patients with a follow-up < 6 months were excluded.Direct UC-related resource use and costs accounting for hospitalizations, outpatient treatment, drug costs according to pharmacy sales prices were reported per patient-year (PY). Results Among 574 UC patients who initiated an advanced therapy, 328 patients (median age: 37 years; female: 52.1%; biologic-naïve: 85.4%) with sufficient follow-up time (median: 12.2 months) were identified. Out of these, 59 patients (19%) were dose-escalated within the first year, whereas 73 patients (22%; anti-TNF: 61; vedolizumab: 12) were found to experience a therapy escalation during the whole follow-up time (average daily dose during maintenance therapy: adalimumab: 5.3 mg, infliximab: 14.6 mg, golimumab: 3.7 mg, vedolizumab: 11.1 mg, tofacitinib: n/a). Total observed direct cost related to UC amounted to €39,514/PY (95%-CI: 37,469-41,558), with €37,369/PY (34,852-39,885; Figure 1) caused by UC-related medication (95%). In comparison, UC-related total direct costs and drug costs for patients without any observable escalation were much lower (€30,425/PY [29,672-31,178]; p-value <0.001 and €28,066/PY [27,230-28,902]; p-value <0.001). Frequency of hospitalizations due to UC (0.3 [0.2-0.5] vs. 0.4 [0.3-0.5]; p-value: 0.947) and gastroenterologist visits (2.1 [1.6-2.6] vs. 2.3 [2.1-2.5]; p-value: 0.361) were similar among both groups. Conclusion Nearly one-fifth of observed patients required therapy escalation in the first year, most likely due to secondary LOR. This results in higher UC-related costs. Payers should consider rates and costs of dose escalations when evaluating the cost-effectiveness of advanced therapies.