Shifting from the treat-to-target to the early highly effective treatment approach in patients with multiple sclerosis - real-world evidence from Germany.

Background: While evidence highlights the effectiveness of initiating disease-modifying therapy with a high-efficacy medication for multiple sclerosis (MS) patients with poor prognostic factors, it remains unclear whether this approach has been adopted by a broad range of MS providers in Germany yet. Objective: To assess the adoption of the early highly effective treatment (EHT) compared to the treat-to-target treatment approach with the option of escalating treatment efficacy over time in Germany based on real-world evidence data. Design: Patient-level pharmacy dispensing data from the Permea platform were analysed from 2020 to 2022. Methods: In total, 29,529 therapy beginners (>18 years) were included to analyse shifts in treatment approaches over time and switching behaviour. Medication classification adhered to the German Society of Neurology guidelines and designated fumarates, glatiramer acetate, teriflunomide and interferons as low-efficacy category 1 medications; cladribine and S1P-modulators as medium-efficacy category 2 medications; and alemtuzumab, natalizumab, ocrelizumab, ofatumumab and rituximab (off-label) as high-efficacy category 3 medications. Results: Our results show that 70.0% of patients redeemed their first prescription for category 1 medication, 16.3% for category 2 and 13.7% for category 3 medications. The proportion of prescriptions filled shifted from 2020 to 2022 with a decrease of 14.7% for category 1 drugs and an increase of 12.5% for category 3 drugs. 93.2% of patients stayed on their initially prescribed medication category. 3.2% of category 1 and 3.7% of category 2 therapy beginners escalated to category 3 medication. 3.4% of category 3 medication users de-escalated their treatment to category 1 or category 2. Conclusion: While most individuals started their treatment according to the treat-to-target approach and remained on their initially prescribed medication category, there has been a steadily increasing shift towards the EHT approach since 2020. These insights demonstrate that, while not officially recommended by German guidelines, MS providers increasingly adopt the EHT approach.

Does overweight influence the prognosis of renal cell carcinoma? Results of a multicenter study.

OBJECTIVES: To assess the impact of overweight on prognosis of renal cell carcinoma patients. PATIENTS AND METHODS: A total of 2030 patients who underwent surgery for renal cell carcinoma from 1990 to 2011 in three University Medical Centers were included in this retrospective analysis. For all patients, height and weight measurements at the time of diagnosis were available for review. The median (mean) follow up was 56.6 months (66.0 months). RESULTS: A low body mass index was significantly associated with poor tumor differentiation, histology, microscopic vascular invasion and metastatic disease at the time of diagnosis. A lower-than-average body surface area - stratified according to the European average for men (1.98 m(2)) and women (1.74 m(2)) - was significantly related to older age, poor tumor differentiation, the histological subtype and microscopic vascular invasion. In addition, a low visceral fat area calculated in a subgroup of 133 evaluable patients was associated with a higher risk of advanced disease (pT3-4 and/or N/M+) at diagnosis. The tumor-specific 5-year survival rate was 71.3, 78.7 and 80.1%, for patients with a body mass index of, <25, 25-30 and ≥30. Multivariate analysis confirmed body mass index as an independent prognostic factor. CONCLUSION: Our findings suggest that overweight represents an independent prognostic factor in renal cell carcinoma patients. Further research should address the question of why obese people have a higher incidence of renal cell carcinoma, but at the same time a significantly better prognosis than other patients, particularly in the case of localized disease.

Obesity is associated with improved survival in patients with organ-confined clear-cell kidney cancer.

OBJECTIVES: Obesity increases the risk of developing renal cell carcinoma (RCC); however, it remains unclear whether obesity is associated with RCC aggressiveness and survival. We assessed whether different body mass index (BMI) levels at the time of surgery had an effect on long-term prognosis of RCC patients. METHODS: We evaluated 1,338 clear-cell RCC patients with complete information about their BMI, who had undergone surgery for renal cell cancer at the University Hospitals in Hannover and Marburg between 1991 and 2005. The mean follow-up was 5.1 years. RESULTS: Underweight, normal weight, pre-obesity, and obesity were diagnosed in 14 (1.0%), 444 (33.2%), 593 (44.3%), and 287 (21.4%) RCC patients, respectively. A lower BMI was significantly associated with higher age, tumor grade, and the rate of metastasis at diagnosis. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 70.9% (pre-obese), 74.0% (obese grad I), and 85.6% (obese grad ≥II) as opposed to 63.8% for patients with a BMI below 25 (p < 0.001). Interestingly, subgroup analysis revealed that the positive association between overweight and survival was found in organ-confined RCC only. CONCLUSION: We identified overweight as an independent prognostic marker of improved cancer specific survival in patients with organ-confined but not advanced RCC. Basic research is required to resolve the dilemma of why, if a higher BMI predisposes to RCC, it concurrently prolongs survival after patients have undergone (partial) nephrectomy.

Urinary collecting system invasion is no independent prognostic factor in renal cell carcinoma.

OBJECTIVES: To assess the specific impact of urinary collecting system (UCS) invasion on the long-term prognosis of patients with renal cell carcinoma (RCC). METHODS: We evaluated 1,678 patients with complete information about UCS invasion of their primary RCC who had undergone renal surgery between 1990 and 2005 in two high volume centers (MH Hannover and Marburg, Germany); the mean follow-up was 5.4 years. RESULTS: Hundred and forty-nine (8.9%) patients demonstrated collecting system invasion. These patients incurred a significant increase in the likelihood of cancer-related death (HR 1.7, 95% CI: 1.4-2.0; P < 0.001), their median 5-year tumor-specific survival rate was 45% as opposed to 73% for patients without UCS invasion (P < 0.001). UCS invasion was significantly associated with tumor stage, grade, lymph node, and visceral metastasis at diagnosis but not with age, gender, histologic subtype, or body mass index. However, using multivariate analysis, UCS invasion disqualified as individual prognostic factor for RCC, neither for localized nor for advanced disease. CONCLUSION: Facing the results of this large trial, we do not support the inclusion of UCS invasion into upcoming TNM staging systems. In contrast, future research should focus on novel molecular markers expressed by the tumor and/or specific immunological characteristics of patients with RCC which could improve prediction of RCC-associated prognosis.

Urinary collecting system invasion in renal cell carcinoma: incidence and long-term prognosis.

OBJECTIVES: Current data on the prognostic impact of urinary collecting system (UCS) invasion by renal cell carcinoma (RCC) are highly conflicting. The aim of the present study was to assess incidence and long-term prognosis of RCC patients with and without UCS involvement. METHODS: We evaluated 780 patients who had undergone renal surgery between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS: Sixty-seven patients (8.6%) demonstrated UCS invasion. These patients had a significant increase in the likelihood of cancer-related death (hazard ratio [HR] 1.9, 95% confidence interval: 1.4-2.7; P = 0.001). Their median 5-year tumor-specific survival rate was 61%, as opposed to 79% for patients without UCS invasion (P = 0.001). UCS invasion was significantly associated with tumor stage, grade, clinical symptoms, lymph node and visceral metastasis at diagnosis, but not with age, gender, histologic subtype or body mass index. However, by means of multivariate analysis, UCS invasion was disqualified as an individual prognostic marker for RCC. CONCLUSION: We do not advocate the inclusion of UCS invasion into upcoming Tumor-Nodes-Metastasis staging systems. In contrast, future research should focus on the prognostic role of novel molecular tumor markers and/or specific immunological characteristics of RCC patients.

Overweight is associated with improved cancer-specific survival in patients with organ-confined renal cell carcinoma.

OBJECTIVES: Overweight/obesity is known to increase the risk of developing renal cell carcinoma (RCC). However, data on the prognostic impact of overweight in RCC is still conflicting. We assessed whether different body mass index (BMI) levels at the time of surgery had an effect on the long-term prognosis of RCC patients. METHODS: We evaluated 771 patients, with complete information about their BMI, who had undergone renal surgery for RCC between 1990 and 2005 at the authors' institution; the mean follow-up was 5.48 years. RESULTS: Underweight, normal weight, pre-obesity, and obesity were diagnosed in 4 (0.5%), 239 (31%), 356 (46.2%), and 172 (22.3%) RCC patients, respectively. Overweight (BMI >25) was significantly associated with younger age (P = 0.004) and positive nodal status (P = 0.04) but not with tumor stage, grade, visceral metastasis, gender, histological subtype, or tumor-related symptoms. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 80% as opposed to 72% for patients with a BMI below 25 (P = 0.003). Interestingly, subgroup analysis revealed that the positive association between overweight and survival was even more pronounced in organ-confined (P < 0.001) RCC, but no correlation was observed in advanced disease (P = 0.23). CONCLUSION: We were able to identify overweight as an independent prognostic marker of improved tumor-specific survival in patients with organ-confined RCC. Basic research is required to resolve the dilemma of why, if a higher BMI predisposes to RCC, it concurrently prolongs survival after patients have undergone (partial) nephrectomy.