Characteristics and outcomes of peripheral neuropathic pain patients with repeated applications of high-concentration capsaicin cutaneous patch: Results of a retrospective chart review in Germany.

OBJECTIVE: The aim of this study was to evaluate patient characteristics, concomitant analgesic medication, and pain intensity in a real-world setting in Germany, focusing on the repeated application of high-concentration capsaicin patch (HCCP) for neuropathic pain. DESIGN: Data were collected from electronic medical records of patients who received at least two HCCP treatments between January 2011 and July 2022. Subgroup analyses were performed based on the number of HCCP treatments, age groups, and specific neuropathic pain conditions. SETTING: The study was conducted at an outpatient pain center in Wiesbaden, Germany. SUBJECTS: The study included 97 patients, primarily diagnosed with neuropathic back pain, postoperative or post-traumatic neuropathic pain, and postherpetic neuralgia. METHODS: The daily dose of concomitant medications (eg, opioids and anticonvulsants) at the start of capsaicin therapy was compared with the average within 2 years of capsaicin therapy. The last observation carried forward method was used if HCCP treatment was discontinued before the end of the 2-year period. RESULTS: The majority of patients received concomitant medications, with opioids, anticonvulsants, and antidepressants being the most common. The average daily morphine equivalent dose decreased significantly during HCCP treatment. Pain intensity at baseline was generally high, but substantial improvements were observed in patients who received at least three HCCP applications. CONCLUSIONS: This study provides evidence for the effectiveness of HCCP treatment in reducing pain intensity and concomitant opioid use in patients with neuropathic pain. Further research is needed to explore the long-term outcomes and optimal treatment regimens for different patient populations.

Prognostic impact of fractional flow reserve measurements in patients with acute coronary syndromes: a subanalysis of the FLORIDA study.

Randomized trials suggest benefits for fractional flow reserve (FFR)-guided vs. angiography-guided treatment strategies in well-defined and selected patient cohorts with acute coronary syndromes (ACS). The long-term prognostic value of FFR measurement in unselected all-comer ACS patients, however, remains unknown. This subanalysis of the Fractional FLOw Reserve In cardiovascular DiseAses (FLORIDA) study sought to investigate the long-term effects of FFR in the management of lesions in patients with acute coronary syndrome (ACS). FLORIDA was an observational all-comer cohort study performed in Germany, that was population-based and unselected. Patients enrolled into the anonymized InGef Research Database presenting with ACS and undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Patients were stratified into either the FFR-guided or the angiography-guided treatment arm, based on the treatment received. A matched cohort study design was used. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), a composite of death, non-fatal myocardial infarction (MI), and repeat revascularization. Follow-up time was 3 years. Rates of 3-year mortality were 10.2 and 14.0% in the FFR-guided and the angiography-guided treatment arms (p = 0.04), corresponding to a 27% relative risk reduction for FFR in ACS patients. Rates of MACE were similar in both arms (47.7 vs. 51.5%, p = 0.14), including similar rates of non-fatal MI (27.7 vs. 25.4%, p = 0.47) and revascularization (9.9 vs. 12.1%, p = 0.17). In this large, all-comer observational study of ACS patients, FFR-guided revascularization was associated with a lower mortality at 3 years. This finding encourages the routine use of FFR to guide lesion revascularization in patients presenting with ACS.

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture.

AIMS: For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture. MATERIALS AND METHODS: An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare. RESULTS: NInject was cost-effective compared to microfracture (ICER: £5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of £20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: £69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service. LIMITATIONS AND CONCLUSION: This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox.

Long-term cost-effectiveness of matrix-associated chondrocyte implantation in the German health care system: a discrete event simulation.

INTRODUCTION: Cartilage defects in the knee can be caused by injury, various types of arthritis, or degeneration. As a long-term consequence of cartilage defects, osteoarthritis can develop over time, often leading to the need for a total knee replacement (TKR). The treatment alternatives of chondral defects include, among others, microfracture, and matrix-associated autologous chondrocyte implantation (M-ACI). The purpose of this study was to determine cost-effectiveness of M-ACI in Germany with available mid- and long-term outcome data, with special focus on the avoidance of TKR. MATERIALS AND METHODS: We developed a discrete-event simulation (DES) that follows up individuals with cartilage defects of the knee over their lifetimes. The DES was conducted with a status-quo scenario in which M-ACI is available and a comparison scenario with no M-ACI available. The model included 10,000 patients with articular cartilage defects. We assumed Weibull distributions for short- and long-term effects for implant failures. Model outcomes were costs, number of TKRs, and quality-adjusted life years (QALYs). All analyses were performed from the perspective of the German statutory health insurance. RESULTS: The majority of patients was under 45 years old, with defect sizes between 2 and 7 cm2 (mean: 4.5 cm2); average modeled lifetime was 48 years. In the scenario without M-ACI, 26.4% of patients required a TKR over their lifetime. In the M-ACI scenario, this was the case in only 5.5% of cases. Thus, in the modeled cohort of 10,000 patients, 2700 TKRs, including revisions, could be avoided. Patients treated with M-ACI experienced improved quality of life (22.53 vs. 21.21 QALYs) at higher treatment-related costs (18,589 vs. 14,134 € /patient) compared to those treated without M-ACI, yielding an incremental cost-effectiveness ratio (ICER) of 3376 € /QALY. CONCLUSION: M-ACI is projected to be a highly cost-effective treatment for chondral defects of the knee in the German healthcare setting.

Patients with hereditary angioedema and their treatment patterns in Germany: a Delphi consensus study

Background: Little is known about how many patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) receive on-demand and/or prophylactic treatment and what their clinical features are. Here, we estimated, using Delphi-based consensus, prevalence and treatment patterns in Germany as well as patient features linked to long-term prophylaxis. Materials & Methods: Eight experts, who together treat approximately 75% of all German HAE-C1-INH patients, participated in a classic, two-round Delphi survey. Consensus was defined as agreement between at least 75% of participants. Results: Experts agreed that an estimated 1,350 patients in Germany have HAE-C1-INH, i.e. 1.62 per 100,000. One in four patients was estimated to receive long-term prophylaxis. Patient features linked to the use of prophylactic treatment included reduced quality of life, frequent swellings and swellings that affect the upper airways, and >two attacks per month. Conclusion: The rate of prophylactic treatment in Germany is low, but is expected to increase. The level of disease activity and its impact and control are and should be considered in the choice for prophylactic treatment.

Incidence, Prevalence, and Real-World Treatment Patterns in Chronic Myeloid Leukemia: Results from a Population-Representative German Claims Data Analysis.

INTRODUCTION: Real-world data on usage of 1st-, 2nd-, and 3rd-generation tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML) are scarce. This study therefore aimed to analyze the use of different TKIs used in 1st- and 2nd-line treatment and the frequency of TKI switches in CML. METHODS: This observational study was based on the InGef research database, an anonymized representative claims dataset in Germany (n = 4 million). An incidence and prevalence patient CML cohort was followed for 5 and 3 years. Analyses regarding incidence, prevalence, and therapy distribution were performed descriptively. RESULTS: 151 patients were included in the incidence and 636 patients in the prevalence cohort. This resulted in an incidence of 1.8 (95% confidence interval [CI]: 1.34-2.20) and a prevalence of 14.9 (95% CI: 13.70-16.03) per 100,000 inhabitants. For the incidence cohort, data on 1st-line therapy were available for 124 patients and distributed across imatinib (N = 52), nilotinib (N = 44), dasatinib (N = 12), chemotherapies as hydroxycarbamide (N = 11), and ponatinib/bosutinib (N = 5). Twenty-six percent of patients switched TKI therapy at least once in 3 years. In the prevalence cohort, 423 patients (66.5%) had claims on existing or newly emerged cardiovascular diseases (CDs). No significant differences (p = 0.32) between TKIs in patients with CD were found. DISCUSSION: Every fourth patient switched TKI therapy within the first 3 years after treatment initiation. Switches were more likely when hints of disease progression or intolerability were observable in the database.

Prevalence, incidence, and health care utilization of patients with narcolepsy: a population-representative study.

STUDY OBJECTIVES: Previous estimated prevalence of narcolepsy in Europe was 47 patients per 100,000 persons, with a yearly incidence of 0.64-1.37 per 100,000. However, analyses of representative datasets from large cohorts are limited. This study aimed to estimate the population-based diagnostic prevalence and incidence of narcolepsy in Germany and to describe these patients and their health care resource utilization. METHODS: This study used the InGef research database, an anonymized representative dataset of 4 million persons covered by statutory health insurance in Germany. Patients with confirmed narcolepsy diagnoses in 2018 were included. Mid-p-exact tests were used to calculate 95% confidence intervals. Patients with narcolepsy diagnoses and narcolepsy-targeting therapy in 2014-2018 were included to describe health care resource utilization in the year prior to diagnosis. RESULTS: In 2018, diagnostic prevalence was estimated as 17.88 (95% confidence interval 16.45-19.40) and 12-month incidence as 0.79 (0.52-1.15) per 100,000 persons. Forty-six percent of patients were in psycho-behavioral therapeutic treatment and 61% of employees had sick leave days. One in three patients was hospitalized for any cause; 28% received antibiotics. CONCLUSIONS: Diagnostic prevalence was lower, but incidence was consistent with previous reports, although previous estimates may diverge in terms of age/sex distributions. Patients showed a substantial utilization of health care resources, including sick leave and hospitalization. Almost half the patients underwent psycho-behavioral treatment in the year prior to diagnosis, which might indicate a high burden of psychiatric symptoms. The increased use of antibiotics could indicate more frequent infections than in the general population. CITATION: Kallweit U, Nilius G, Trümper D, Vogelmann T, Schubert T. Prevalence, incidence, and health care utilization of patients with narcolepsy: a population-representative study. J Clin Sleep Med. 2022;18(6):1531-1537.

Oral or Topical Pain Therapy-How Would Patients Decide? A Discrete Choice Experiment in Patients with Peripheral Neuropathic Pain.

To ensure an adequate pain therapy with high patient adherence, it is necessary to know and consider patient preferences. A discrete choice experiment was used to obtain patients' preferences regarding treatment with systemic or topical pain medication. Patients with peripheral neuropathic pain (pNP) were recruited in two pain-focused practices in Germany. To identify relevant attributes of topical or systemic pain medication, a literature review and face-to-face interviews with experts for pain treatment were conducted. The attributes used in the choice scenarios were noticeable onset of effect, time spent in medical office, risk of systemic and local side effects, and impairment of daily life with regard to sleep quality and sexuality. The model was estimated with a mixed multinomial logit regression model. The study included 153 participants suffering from moderate to severe pNP. Most important attributes from patient's perspective was noticeable onset of effect (odds ratio 2.141 [95% confidence interval 1.837 to 2.494]), followed by risk of systemic side effects (2.038 [1.731 to 2.400]) and risk of sexual dysfunction (1.839 [1.580 to 2.140]), while risk of local side effects regarding skin ranked fourth (1.612 [1.321 to 1.966]). The impairment of sleep quality was also significant but less important (1.556 [1.346 to 1.798]). Local side effects were more likely to be accepted than systemic side effects. The risk of sexual dysfunction as a side effect of treatment is very important for patients, although it has received little attention in the literature.

All-cause mortality in patients with long-term opioid therapy compared with non-opioid analgesics for chronic non-cancer pain: a database study.

BACKGROUND: Hitherto only studies with selected populations have found an increased all-cause mortality of some selected opioids compared to selected non-opioids for chronic non-cancer pain (CNCP). We have examined the all-cause mortality for CNCP associated with all established opioids compared to non-opioid analgesic therapy (anticonvulsants, antidepressants, dipyrone, non-steroidal agents). METHODS: The study used the InGef (Institute for Applied Health Research Berlin) database which is an anonymized healthcare claims database including 4,711,668 insured persons who were covered by 61 German statutory health insurances between 2013 and 2017.The health insurance companies are the owners of the database. All-cause mortality was determined from death certificates. Adjusted hazard ratios (HRs) including age, gender, comorbidity index, and propensity score as covariates and risk differences (RD) in incidence of death between patients with long-term opioid therapy (LTOT) and control-drug therapy were calculated. RESULTS: The mean age of participants was 66 years; 55% were women. There were 554 deaths during 10,435 person-years for the LTOT patients, whereas there were 340 deaths during 11,342 person-years in the control group. The HR for all-cause mortality was 1.59 (95% CI, 1.38-1.82) with a risk difference of 148 excess deaths (95% CI 99-198) per 10,000 person-years. The elevated risk of death for LTOT was confined to the out-of-hospital deaths: LTOT patients had 288 out-of-hospital deaths during 10,435 person-years (276 per 10,000 person-years) whereas there were 110 deaths during 11,342 person-years (97 per 10,000 person-years) in the control group. HR was 2.29 (95% CI 1.86, 2.83). Although our propensity score matching model indicated a good classification, residual confounding cannot be fully excluded. The opioid group had a higher prevalence of heart failure and a higher use of anti-thrombotic and antiplatelet agents and of psycholeptics. CONCLUSIONS: LTOT for CNCP compared to non-opioid analgesics was associated with an increased risk for all-cause mortality. When considering treatment options for patients with CNCP, the relevant risk of increased all-cause mortality with opioids should be discussed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03778450, Registered on 7 December 2018.

Treatment Costs of Matrix-Associated Autologous Chondrocyte Implantation Compared With Microfracture: Results of a Matched-Pair Claims Data Analysis on the Treatment of Cartilage Knee Defects in Germany.

BACKGROUND: Articular cartilage damage is caused by traumatic sport accidents or age-related degeneration and might lead to osteoarthritis, which represents a socioeconomic burden to society. Cartilage damage in the knee is commonly treated surgically with microfracture (MFX) or matrix-associated autologous chondrocyte implantation (MACI). PURPOSE: To quantify the initial and follow-up costs associated with MFX and MACI treatments from the viewpoint of statutory health insurance in Germany. STUDY DESIGN: Economic decision analysis; Level of evidence, 2. METHODS: This comparative study was based on an anonymized representative claims data set of 4 million patients covered by statutory health insurance in Germany. Patients undergoing outpatient or inpatient treatment with MACI or MFX for cartilage damage in the knee between January 1, 2012, and December 31, 2013, were included and evaluated over 5 years. Groups (MACI and MFX) were adjusted via propensity score matching before initial treatment. The matched groups were compared regarding their outpatient, inpatient, pharmaceutical, and other costs during the 5-year period. RESULTS: In total, 127 patients per group were analyzed (59.1% male, 40.9% female; mean age, 37 years). In the year of the initial surgical procedure, costs were €14,804.13 in the MACI group and €5458.59 in the MFX group. In years 2 and 3 after initial surgery, treatment costs were comparable between patients treated with MACI (€2897.97 and €2114.87, respectively) and MFX (€2842.66 and €1967.42, respectively), with slightly higher treatment costs for those treated with MACI. In years 4 and 5 after surgery, costs were less in patients treated with MACI (€2154.79 and €1478.08, respectively) than in those treated with MFX (€2232.57 and €2061.63, respectively). Costs related to revision surgery were, on average, €3732 for MACI and €3765 for MFX. Thus, additional costs in years with revision surgery were €1672 for MACI and €1915 for MFX. CONCLUSION: This was the first study to analyze a large representative population claims database with propensity score matching, and results indicated that follow-up costs of patients treated with MACI and MFX began to converge over time. We found that total costs for MACI were higher than for MFX but that additional costs for MACI were lower than previously reported. Perceived morbidity may have little to do with cost.

Matrix-Associated Chondrocyte Implantation Is Associated With Fewer Reoperations Than Microfracture: Results of a Population-Representative, Matched-Pair Claims Data Analysis for Cartilage Defects of the Knee.

BACKGROUND: Symptomatic cartilage defects of the knee are commonly surgically treated by microfracture (MFX) or matrix-associated chondrocyte implantation (M-ACI). Several randomized controlled trials have compared MFX and M-ACI, showing a tendency to lower reoperation rates for M-ACI, but results vary widely between studies. PURPOSE: To compare reoperation rates after MFX and M-ACI in cartilage defects of the knee outside clinical trials in a representative sample of the population. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study was based on anonymized, population-representative claims data of 4 million insured persons in Germany. Patients who underwent MFX or M-ACI for cartilage defects of the knee with a follow-up of 2 years were compared. The primary endpoint was the need for a reoperation, defined as a claim for a second surgical procedure from the same patient at the knee joint (27 procedure codes), meniscus and cartilage (35 procedure codes), or patella (102 procedure codes) or the need for knee replacement (11 procedure codes). Group comparisons were performed using log-rank tests, with a 2-sided P value of <.05 to indicate significance. For adjusted analysis, propensity score matching was applied. Age, sex, comedications, and comorbidities were used as matching parameters. RESULTS: A total of 6425 patients fulfilled the inclusion criteria: 6273 treated with MFX and 152 treated with M-ACI (mean age, 53 and 36 years, respectively). In the 2 years after treatment, 1271 patients in the MFX group needed a reoperation compared with 19 in the M-ACI group (20.3% vs 12.5%, respectively; P = .0199). For adjusted analysis after propensity score matching, 127 patients per group were analyzed. Their mean age was 37 years. At the end of the second follow-up year, 28 and 16 patients needed reoperations in the MFX and M-ACI groups, respectively (22.0% vs 12.6%, respectively; P = .0498). CONCLUSION: This study used a representative sample of the population and a broad definition of a reoperation, thus expanding evidence from clinical trials. We found a significant advantage of M-ACI in reoperation rates 2 years after treatment. After adjusting for age, sex, comedications, and comorbidities, M-ACI still showed significantly lower reoperation rates after 2 years.

Guideline-recommended vs high-dose long-term opioid therapy for chronic noncancer pain is associated with better health outcomes: data from a representative sample of the German population.

Recent evidence-based guidelines for long-term opioid therapy (LTOT) for chronic noncancer pain (CNCP) have defined daily morphine equivalent doses (MEQ/d) that require particular caution. The recommendation for a threshold MEQ/d is based on North American studies that have demonstrated negative health outcomes associated with high-dose LTOT for CNCP. We have conducted a retrospective cross-sectional study using an anonymized German health claims database, including 4,028,618 persons insured by 69 German statutory health insurances, representative of age and sex for the German population in 2014. Those receiving German guideline-recommended opioid treatments (dose <120 mg MEQ/d) for CNCP were compared with those receiving high-dose LTOT (≥120 mg MEQ/d) for selected health outcomes (risky opioid prescribing; hospital admissions due to diagnoses indicative of abuse/addiction of prescribed opioids; and health costs). The prevalence of LTOT for CNCP was 0.8%, with 9.9% receiving high-dose LTOT. Those receiving German guideline-recommended opioid treatments vs those receiving high-dose LTOT differed for the following parameters: risky opioid prescribing (combination with tranquilizers) (11.1% vs 14.3%; P < 0.001), hospital admissions because of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxication by narcotic agents (1.6% vs 2.9%; P < 0.001), and total health costs (7259 vs 10,732 Euro; P < 0.001). The difference in annual costs between the 2 groups was largely due to differences in pharmaceutical costs in the outpatient setting (2282 vs 5402 &OV0556;; P < 0.001). These data confirm recommendations for a threshold MEQ/d for CNCP as recommended by recent opioid prescribing guidelines for CNCP.