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Thomas Wilke,1 Nils Picker,2 Sabrina Müller,2 Anna Stürmlinger,3 Barthold Deiters,4 Axel Dittmar,1 Jens Aberle,5 Maximilian Gabler3 1IPAM e.V., Wismar, Germany; 2Ingress-Health HWM GmbH, Wismar, Germany; 3Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany; 4GWQ ServicePlus AG, Düsseldorf, Germany; 5Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, GermanyCorrespondence: Nils Picker, Ingress-Health HWM GmbH, Alter Holzhafen 19, Wismar, 23966, Germany, Tel +49 3841 758 1013, Fax +49 3841 758 1011, Email nils.picker@ingress-health.comPurpose: 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 score-matched 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: n1/n2 = 3100/3100 and EMPA versus GLP-1-RA: n3/n4 = 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 EMPA (€ 6851 [6183– 7518] versus € 4895 [4345– 5445]).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.Keywords: type 2 diabetes mellitus, sodium-glucose cotransporter-2 inhibitor, DPP-4 inhibitors, GLP-1 receptor agonists, healthcare costs

Pharmacotherapy options for chronic lymphocytic leukaemia (CLL) have expanded significantly in recent years. These options include chemotherapy, chemoimmunotherapy and signalling pathway inhibitors. A notable shift in the treatment landscape began with the widespread adoption of ibrutinib in 2016. This analysis of claims data focuses on understanding how the use of novel therapies has evolved in clinical practice over the past decade in Germany. Anonymized claims data (2010-2022) from German statutory health insurance was used, covering patient demographics, treatments, and prescriptions. The study population included patients with two confirmed CLL diagnoses. Treatment patterns were analysed, and survival outcomes were compared using time-to-event analyses. In the analysed cohort of 2983 incident CLL patients, 1041 started first-line therapy between 2011 and 2022, with a median duration of 18 months from diagnosis to the first prescription. Chemoimmunotherapy, the predominant 1L therapy until 2019, decreased significantly, while targeted therapy usage increased from 3% in 2015 to 77% in 2022. Targeted therapies became dominant in patients receiving treatment for relapsed or refractory disease after 2016. Median treatment durations were: 122 days for chemo, 176 days for chemo-immuno, and 373 days for targeted therapy. The overall survival for patients diagnosed in or after 2016 was significantly better (hazard ratio 0.56, 95% confidence interval, 0.44-0.69)). The adoption of targeted therapies like ibrutinib and venetoclax has transformed CLL treatment in Germany, leading to improved patient outcomes. Additionally, we demonstrate successful adherence to evolving clinical guidelines., Competing Interests: Barthold Deiters is employed at the GWQ ServicePlus AG, which was founded and is owned by a group of health insurance companies. Timm Volmer, Hannes Wartmann and Anna Kabilka are employed by SmartStep Data Institute, which works as a scientific partner institute to SmartStep Consulting, a private sector entity specialized in market access consulting. Furthermore, the authors declare that they have no competing interests., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Aim: To determine the real-world treatment patterns and recurrence of cardiovascular-related procedures and hospitalizations in patients at very-high atherosclerotic risk., Methods: In this retrospective observational study, atherosclerotic cardiovascular disease (ASCVD)-related procedures and hospitalizations, and lipid-lowering therapy (LLT) medication data were assessed in adults with hypercholesterolemia or mixed dyslipidemia with an incident ASCVD-related procedure using health claims data from the German AOK PLUS (2010-2020) and GWQ ServicePlus databases (2013-2019). Differences in time-to-first event between LLT and non-LLT groups were assessed using a propensity score matched (PSM) comparison., Results: Following the index procedure, approximately 20% of patients had at least one subsequent ASCVD-related procedure in the first 12 months, and approximately 50% had an ASCVD-related re-hospitalization. The total proportion of patients prescribed LLT prior to the index ASCVD-related procedure was approximately 30%. In the index procedure quarter, 68% of patients received a prescription for LLT (non-intensified LLT: 63%; intensified LLT: 5%); 32% did not receive any LLT. PSM comparative analysis showed a reduced risk of time to all-cause death in the LLT versus non-LLT group (AOK PLUS, hazard ratio [HR] 0.62 [95% confidence interval {CI}: 0.60-0.65]; GWQ ServicePlus, HR 0.46 [95% CI: 0.43-0.49])., Limitations: Limitations inherent to retrospective health claims data including bias owing to unobservable confounders; potential incomplete capture of patients at "very-high atherosclerotic risk" given the defined nature of categorization criteria used in the study., Conclusion: This real-world study demonstrates that a substantial proportion of very-high-risk patients have recurrent ASCVD-related hospitalizations and events following an initial procedure. Many patients receive no LLT after an ASCVD-related procedure, and among those who do, a large percentage receive only non-intensified LLT. These findings have implications for mortality, morbidity, and healthcare costs and warrant further investigation.

Aims: This retrospective claims data study characterized real-world treatment patterns, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) in Germany., Materials and Methods: Continuously insured adults with incident mUC diagnosis (=index; ICD-10 : C65-C68/C77-C79) in 2015-2019 were identified from two German claims databases. Patients who received first-line (1 L) treatment within 12 months of index were divided into three mutually exclusive sub-cohorts: platinum-based chemotherapy (PB-CT), non-PB-CT, and immunotherapy (IO). Patient characteristics were assessed during a 24-month baseline period; treatments, HCRU, and costs (of the health insurance fund) per patient-year (ppy) were described during 12-month follow-up., Results: We identified 3,226 patients with mUC (mean age, 73.8 years; male, 70.8%; mean Elixhauser Comorbidity Index, 17.6); 1,286 (39.9%) received 1 L treatment within 12 months of index. Of these, 825 (64.2%) received PB-CT, 322 (25.0%) non-PB-CT, and 139 (10.8%) IO. On average, treated patients had 5.1 hospitalizations ppy. Most UC-related hospitalizations ppy were observed in the PB-CT cohort (5.8), followed by the non-PB-CT (4.2) and IO (2.3) cohorts. Mean UC-related hospitalization costs ppy were €22,218 in the treated cohort, €24,294 in PB-CT, €19,079 in IO, and €18,530 in non-PB-CT cohorts. Cancer-related prescription costs ppy averaged €6,323 in treated patients, and €25,955 in IO, €4,318 in non-PB-CT, and €4,270 in PB-CT cohorts., Limitations: We recognized limitations in our study's sample selection due to unavailable mUC disease status data. We addressed this through an upstream feasibility study conducted in consultation with clinical experts to determine a suitable proxy. Proxies were also used to delineate treatment lines, switches, and discontinuations due to data absence. Furthermore, due to data restrictions, collective dataset analysis was not possible, prompting a meta-analysis for pooled results., Conclusions: The study shows that mUC is associated with significant HCRU and costs across different types of 1 L systemic therapy.

Aim: This study assessed real-world treatment in patients with metastatic urothelial carcinoma (mUC) in Germany. Materials & methods: Patients diagnosed with mUC from 2015 to 2019 were identified in two claims databases: AOK PLUS and GWQ. Results: 3226 patients with mUC were analyzed; 1286 (39.9%) received systemic treatment within 12 months of diagnosis (platinum-based chemotherapy: 64.2%). Factors associated with receiving treatment were: younger age, male sex, less comorbidity and recent diagnosis. In AOK PLUS and GWQ populations, unadjusted median overall survival (interquartile range) from diagnosis in treated patients was 13.7 (6.8-32.9) and 13.8 (7.1-41.7) months, and in untreated patients was 3.0 (1.2-10.8) and 3.6 (1.2-18.8) months, respectively. Conclusion: A significant proportion of patients with mUC in Germany receive no systemic treatment.

Introduction: CAR T-cell therapy has emerged as a promising new immuno-oncology treatment that engages the patient's immune system to fight certain hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). In the European Union (EU), CAR T-cell therapies have been approved for relapsed/refractory (R/R) DLBCL patients since 2018, but patient access is often still limited or delayed. This paper is aimed at discussing challenges to access and possible solutions in the largest four EU countries., Methods: The analysis relied on literature review, market data collection, since homogeneous data coming from registries were not available, and discussion with experts coming from all four countries., Results: We calculated that in 2020, between 58% and 83% of R/R DLBCL patients (EMA approved label population) or between 29% and 71% of the estimated medically eligible R/R DLBCL patients, were not treated with a licensed CAR T-cell therapy. Common challenges along the patient journey that may result in limited access or delays to CAR T-cell therapy were identified. These include timely identification and referral of eligible patients, pre-treatment funding approval by authorities and payers, and resource needs at CAR T-cell centers., Discussion: These challenges, existing best practices and recommended focus areas for health systems are discussed here, with the aim to inform necessary actions for overcoming patient access challenges for current CAR T-cell therapies as well as for future cell and gene therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Canales Albendea, Canonico, Cartron, Deiters, Jommi, Marks, Rioufol, Sancho Cia, Santoro and Wagner-Drouet.)

Objectives: Direct oral anticoagulants (DOACs) were introduced based on randomised controlled trials (RCTs) comparing them to vitamin-K-antagonist (VKA) warfarin. In Germany, almost exclusively phenprocoumon is used as VKA. RCTs with phenprocoumon being absent we analysed the benefits and harms of DOACs and phenprocoumon for patients with atrial fibrillation (AF) in a real-world setting., Design: In a retrospective observational cohort study, claims data covering inpatient and outpatient care from 2015 to 2019 were analysed by Cox regression and propensity score matching (PSM)., Setting: Data from a group of small-sized to medium-sized health insurance companies in Germany., Participants: We analysed datasets of 71 961 patients with AF and first prescription of phenprocoumon (n=20 179) or DOAC in standard dose (n=51 782). Patients with reduced dose of DOACs were excluded (n=21 724)., Outcome Measures: Outcomes were thromboembolic events, major bleeding and death during a 12-month follow-up period., Results: The regression analysis widely showed similarity between phenprocoumon and standard dose DOACs regarding effectiveness and safety. There were only three statistically significant differences: a lower bleeding risk with composite DOACs and apixaban (HR (95% CI) = 0.67 (0.59 to 0.76) and 0.54 (0.46 to 0.63), respectively) and a higher risk of death with rivaroxaban (1.21 (1.10 to 2.34)). The analysis after PSM was consistent with the first two results regarding composite DOACs and apixaban (number needed to treat, NNT 101 and 78) and showed a lower bleeding risk with rivaroxaban (NNT 156). Absolute differences were small., Conclusions: The small superiority or non-inferiority of DOACs over warfarin seen in the RCTs might not translate into relevant advantages of DOACs over phenprocoumon. To confirm the hypothesis, an RCT with phenprocoumon is needed. Next to the safety and effectiveness assessments other factors might also play a substantial role in the decision on the right OAC for stroke prevention., Competing Interests: Competing interests: BD and FK are employees of the GWQ ServicePlus AG owned by insurance companies. There are no other conflicts of interest to declare. There was no financial interaction whatsoever between the GWQ ServicePlus AG and the Institute of General Practice nor will it be., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by autoantibodies directed against postsynaptic antigens of the neuromuscular junction. Over the last decades, increasing incidence and prevalence rates have been reported. Epidemiological data on prevalence and incidence in Germany are lacking. Furthermore, the MG treatment landscape is rapidly changing due to the continued approval of novel monoclonal antibodies., Method: This is a retrospective study assessing incidence, prevalence, and hospitalization rates of MG as well as treatment patterns in Germany over 10 years based on medical claims data covering 6.1 million insured persons., Results: Between 2011 and 2020, the prevalence rate of MG increased from 15.7 to 28.2 per 100,000 person-years. The age-adjusted incidence rate was 2.8 per 100,000 person-years within the study period (95% confidence interval, 2.43-3.22) and decreased dramatically in 2020, the year of the COVID-19 pandemic. Similarly, the hospitalization rate fluctuated within the study period but reached an overall low of 8.3% in 2020 (mean hospitalization rate 11.5%). Treatment patterns showed that most MG patients are treated with base therapy. However, crisis intervention is necessary for 2-5% of MG patients, and therapeutic monoclonal antibodies, including rituximab and eculizumab, are increasingly used., Conclusion: This is the first study on MG prevalence and incidence rates in Germany. Data show an increase in prevalence by 1.8-fold over 10 years. Decreasing incidence and hospitalization rates in 2020 hint at the impact of the COVID-19 pandemic. Treatment patterns in MG are changing with the advent of therapeutic monoclonal antibodies in this indication., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The positioning of new biologic agents for the treatment of Crohn's disease (CD) following failure of initial anti-tumor necrosis factor (anti-TNF) therapy remains a challenge in the real world., Objectives: This study aims to investigate the real-world outcomes associated with the sequential use of biologics in CD patients that newly initiate anti-TNFs, specifically comparing those that switch to another anti-TNF versus biologics with other modes of action., Design: Retrospective cohort study., Methods: We identified CD patients who newly began anti-TNF therapy between 1 October 2014 and 31 December 2018 using two German claims databases. Patients were classified as within-class switchers (WCS) if they switched to another anti-TNF or outside-class switchers (OCS) if they switched to vedolizumab (VDZ) or ustekinumab (UST). To compare WCS and OCS, baseline covariates were adjusted through inverse probability of treatment weighting (IPTW), and time-to-event analyses were performed using Cox Proportional Hazard regressions. Results from both databases were meta-analyzed using an inverse variance model., Results: Overall, 376 prevalent adult CD patients who initiated anti-TNFs and switched to another biologic were identified. After IPTW, there were 152 and 177 patients in the WCS and OCS group, respectively. WCS were more likely to receive prolonged corticosteroid therapy [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.17-2.27, p  = 0.004], switch a second time to a different biologic (HR: 2.44, 95% CI: 1.63-3.66, p  < 0.001), and discontinue treatment (HR: 1.71, 95% CI: 1.25-2.34, p  = 0.001) than OCS., Conclusion: This study suggests that CD patients exhibit more favorable outcomes when switching outside the anti-TNF class to VDZ or UST after initial anti-TNF failure than switching to a second anti-TNF. With loss of response to anti-TNFs as a concern in the real world, comparative evidence from claims data assessing sequential use of biologics can help optimize treatment algorithms of patients after anti-TNF failure., Competing Interests: EZ and BAF are employees of Cytel. The work of Cytel was sponsored by Janssen-Cilag. AB, RN, IB, JNB, MLB, JL, and AP are employees of Janssen-Cilag. UM is an employee of AOK PLUS and declares no conflicts of interest. BD is an employee of GWQ ServicePlus AG and declares no conflicts of interest. BB has received consulting fees from Abbvie, MSD, Shire, Ferring, UCB, Hospira, Takeda, Movetis, Shield Therapeutics, Pfizer, Biogen, Janssen, Hexal, Cellgene, Boehringer, Allergan, Galapagos, and Arena; provided speeches/lectures for Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB, Shield Therapeutics, Pfizer, Celltrion, Takeda, Janssen, Mundipharma, and Arena; and received research grants from Abbvie, Ferring, UCB, Given Imaging, Janssen, Takeda, Pfizer, and Galapagos. TW has received honoraria from several pharmaceutical/consultancy firms, for example, Novo Nordisk, Abbvie, Merck, GSK, BMS, LEOPharma, Bayer, Boehringer Ingelheim. MG is an employee of Cytel and staff member of IPAM e.V., (© The Author(s), 2022.)

Background: For stroke prevention in patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) have been increasingly prescribed instead of vitamin-K-antagonists (VKA). For some patients a lower dosage of DOACs (ld-DOACs) is recommended. Ld-DOAC prescribing seems to be common, although previous studies did not show clear superiority of ld-DOACs over warfarin. In Germany, phenprocoumon is used almost exclusively as VKA. Randomized controlled trials comparing DOACs and phenprocoumon in the general population of patients with AF do not exist. Therefore, we aimed to compare ld-DOACs and phenprocoumon in a real-world setting in Germany., Methods: In a retrospective observational cohort study, claims data from a group of small to medium-sized health insurance companies were analysed. Risks for the outcomes thromboembolism, death and major bleeding were estimated by Cox regression. Out of 93,685 patients with atrial fibrillation and a first prescription of an oral anticoagulant, 20,179 receiving VKA and 21,724 ld-DOACs (29.6% of all DOAC patients) were included. For the sensitivity analysis phenprocoumon was compared to the five ld-DOAC groups (ld-apixaban, ld-dabigatran, ld-edoxaban, ld-rivaroxaban, and the composite of all ld-DOACs) after propensity-score matching., Results: Phenprocoumon was associated with statistically significant fewer thromboembolic events (HR = 1.29, 95% CI [1.13, 1.48], p < .001) and deaths (HR = 1.52, 95% CI [1.41, 1.63], p < .001) and a non-significant higher bleeding risk (HR = 0.89, 95% CI [0.79, 1.00], p = .051) than composite ld-DOAC. Regarding the subgroups, only patients with ld-apixaban had a statistically significant higher risk for thromboembolic events (HR = 1.42, 95% CI [1.21, 1.65], p < .001) and a lower bleeding risk (HR = 0.75, 95% CI [0.65, 0.86], p < .001). Ld-apixaban, ld-edoxaban, and ld-rivaroxaban were associated with a higher risk of death. The sensitivity analysis confirmed these associations., Conclusion: Phenprocoumon seems to be superior to ld-DOACs for patients with AF. As a hypothesis phenprocoumon might turn out to be the wiser choice for high-risk patients with AF as compared to ld-DOACs, especially regarding thromboembolic events and death. Therefore, RCTs comparing ld-DOACs with phenprocoumon are needed., (© 2022. The Author(s).)

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system which causes recurrent relapses, resulting in blindness, paralysis, and spinal cord damage. This study sought to explore the real-world burden, treatment, and cost of NMOSD in Germany using claims data., Methods: Our study consisted of a retrospective analysis of two anonymized health insurance datasets covering around 9 million patients in Germany from 01/01/2013 to 31/12/2019. NMOSD patients were identified using inpatient and outpatient International Classification of Diseases, Tenth Revision (ICD-10) diagnoses of neuromyelitis optica (NMO; G36.0) and relevant symptom codes. Active periods of disease were identified based on relapse events (including hospitalizations and acute treatment); healthcare resource utilization (HCRU) and direct costs were allocated to active and inactive periods based on treatment dates. Propensity score matching was used to compare HCRU and cost outcomes among patients with and without NMOSD., Results: Overall, 130 patients were identified as having NMOSD (mean age: 46.84 years; 58% female). NMOSD patients recorded 16.52 active and 348.48 inactive days per patient year (PPY). HCRU and associated costs were approximately tenfold higher during active periods than during inactive periods, with the largest share of the cost difference driven by hospitalizations (€6424.09/€259.10 per active/inactive month) and outpatient drug prescriptions (€412.83/€271.58). Direct healthcare costs incurred by patients with NMOSD (€12,913.28 PPY) were approximately threefold higher than those incurred by patients without NMOSD (€4667.66 PPY). Costs of hospitalization (€6448.32/€1937.64 PPY) and outpatient prescriptions (€3335.67/€1037.64 PPY) contributed most strongly to the difference., Conclusion: Patients with NMOSD consume substantial healthcare resources and incur heavy costs during active disease phases. This study captured direct measurable healthcare costs and likely underestimates the real societal/emotional burden on patients and their families. Nevertheless, prevention of acute relapses represents one compelling strategy to minimize the economic burden of NMOSD in Germany., (© 2021. The Author(s).)

Objectives: This study aimed to assess the real-world rates of treatment discontinuation and switching of biologic therapies in patients with inflammatory bowel disease (IBD)., Methods: A retrospective claims data analysis on all continuously insured adult IBD patients with initiation of a biologic therapy was conducted. Observation started with the date of the first prescription of index tumor necrosis factor α-inhibitors (anti-TNFα) or vedolizumab (VDZ) therapy and lasted 12 months. Non-persistence was assumed in case of a switch to another biologic or a treatment gap of >90 days., Results: We included 1,248 IBD biologic treatment starters (502 adalimumab, 77 golimumab, 441 infliximab, 228 VDZ); 837/411 were biologic-naïve (bio-naïve)/ biologic-experienced (bio-experienced). Mean age of bio-naïve/bio-experienced anti-TNFα patients was 39.2/38.1 years (54.9%/56.7% female) and 42.6/37.8 years for VDZ patients (56.3%/54.9% female). Seven hundred and seventy-two patients (61.9%) were persistent with their index biologic therapy after 12 months (61.9%/61.8% bio-naïve/bio-experienced). Percentage of persistent patients was 69.7% for VDZ (65.6%/71.3%) and 60.1% for anti-TNFα (61.4%/55.5%). VDZ was associated with later non-persistence in a multivariable Cox regression analysis (hazard ratio 0.675; p = 0.003) compared to anti-TNFα., Conclusions: Only 60-70% of IBD -patients are still persistent with their biologic therapy after 12 months. VDZ therapy is associated with a higher persistence than anti-TNFα therapy in this analysis., (© 2019 S. Karger AG, Basel.)

Objectives:  This study aimed to describe biologic treatment of German inflammatory bowel disease (IBD) patients, including biologics' dosage, health care resource use, and treatment-associated cost., Methods:  In this retrospective claims data analysis, all continuously insured adult IBD patients (Crohn's disease [CD] or ulcerative colitis [UC]) who started a new therapy with an anti-tumor necrosis factor alpha (anti-TNF-α) or vedolizumab (VDZ) were included. Observation started with the date of the first prescription of index biologic therapy and lasted 12 months., Results:  In the database, 1248 out of 57 296 IBD patients started a biologic treatment of interest (1020 anti-TNF-α, 228 VDZ), and 837 patients were bio-naïve (773 anti-TNF-α, 64 VDZ). The mean age of bio-naïve/bio-experienced anti-TNF-α patients was 39.2/38.1 years (54.9 %/56.7 % female) and 42.6/37.8 years for VDZ patients (56.3 %/54.9 % female). The proportion of patients receiving a maintenance dosage > 150 % compared to SmPC was 15.1 % for Adalimumab, 5.2-39.0 % for Golimumab, 14.7-34.5 % for Infliximab, and 19.7 % for VDZ patients. During the maintenance phase, up to 58.8 % of patients received at least 1 prescription of any CS, and 41.7 %/47.1 % (anti-TNF-α/VDZ) were treated in a hospital due to IBD. The mean IBD-related direct health care cost per patient year was € 30 246 (anti-TNF-α)/ € 28 227 (VDZ) for bio-naïve patients (p = 0.288) and € 34 136 (anti-TNF-α)/ € 32 112 (VDZ) for bio-experienced patients (p = 0.011)., Conclusions:  A substantial percentage of patients receive a high biologic dosage in the maintenance phase. Despite biologic therapy, 30-40 % receive a CS therapy and/or experience at least 1 IBD-associated hospitalization within a year, possibly indicating a remaining disease activity., Competing Interests: Brandes A et al. Biologic treatment and associated cost of IBD in Germany. Thomas Wilke has received honoraria from several pharmaceutical/consultancy companies e. g. Novo Nordisk, Abbvie, Merck, GSK, BMS, LEO Pharma, Astra Zeneca, Bayer, Boehringer Ingelheim, Pharmerit. Antje Groth and Fraence Gottschalk participated in this study as a staff members of IPAM e. V.; the work of IPAM e. V. in this study was sponsored by Takeda Pharma Vertrieb GmbH & Co. KG. Alina Brandes, Boris A. Ratsch and Hans-Dieter Orzechowski are employees of Takeda Pharma Vertrieb GmbH & Co. KG. Andreas Fuchs participated in this study as employee of AOK PLUS; he received consultancy fees and reimbursement of travel costs from the pharmaceutical company Bayer. Barthold Deiters is an employee of GWQ ServicePlus AG and declares no conflict of interest. Bernd Bokemeyer has received consultancy fees and grants from several pharmaceutical companies e. g. Abbvie, MSD, Shire, Ferring, UCB, Given Imaging, Hospira, Takeda, Movetis, Shield Therapeutics, Pfizer, Biogen, Janssen, Hexal, Cellgene, Boehringer Ingelheim, Allergan.Supported by Takeda Pharma Vertrieb GmbH & Co. KG., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Osteoarthrosis is characterized by cartilage erosion, proteolysis of aggrecan and collagen, and disturbed rates of synthesis of aggrecan and hyaluronan by chondrocytes, with hyaluronan over-production being an early reaction. We considered that inhibition of hyaluronan export might prevent subsequent proteoglycan loss and collagen degradation., Methods: To test this hypothesis, we studied a tissue culture model using bovine cartilages explants activated with IL-1alpha to induce osteoarthritic reactions using the phosphodiesterase-5 inhibitors tadalafil, zaprinast and vardenafil., Results: These drugs inhibited hyaluronan export, but they did not inhibit hyaluronan synthase activity. Simultaneously, they inhibited proteoglycan loss and collagen degradation, but not their synthesis. They also reduced the release of gelatinases into the culture media and diffusion of the indicator protein horseradish peroxidase through the cartilage explants. The mechanism of action of these compounds may be through inhibition of hyaluronan exporter multidrug resistance-associated protein 5 (MRP5), because the effective drug concentrations were much higher than required for phosphodiesterase-5 inhibition and intracellular cGMP accumulation., Conclusion: Inhibition of hyaluronan over-production may be an appropriate target to attenuate IL-1-induced reactions in osteoarthritic cartilage.