Management, vaccination status and COVID-19 morbidity of patients with Gaucher disease in Germany during the COVID-19 pandemic.

BACKGROUND: Continuation of standard management of Gaucher disease (GD) has been challenging during the COVID-19 pandemic, resulting in infrequent/missed infusions and follow-up appointments. Little data are available on the consequences of these changes and on the SARS-CoV-2 vaccinations in German GD patients. METHODS: A survey with 22 questions about GD management during the pandemic was sent to 19 German Gaucher centres. It was answered by 11/19 centres caring for 257 GD patients (almost ¾ of the German GD population); 245 patients had type 1 and 12 had type 3 GD; 240 were ≥ 18 years old. RESULTS: Monitoring intervals were prolonged in 8/11 centres from a median of 9 to 12 months. Enzyme replacement therapy (ERT) was changed to home ERT in 4 patients and substituted by oral substrate reduction therapy (SRT) in 6 patients. From March 2020 to October 2021, no serious complications of GD were documented. Only 4 SARS-CoV-2 infections were reported (1.6%). Two infections were asymptomatic and two mild; all occurred in adult type 1, non-splenectomized patients on ERT. Vaccination rate in adult GD was 79.5% (95.3% mRNA vaccines). Serious vaccination complications were not reported. CONCLUSIONS: The COVID-19 pandemic has lowered the threshold for switching from practice- or hospital-based ERT to home therapy or to SRT. No major GD complication was documented during the pandemic. Infection rate with SARS-CoV-2 in GD may rather be lower than expected, and its severity is mild. Vaccination rates are high in GD patients and vaccination was well tolerated.

Cost per response for abatacept versus adalimumab in patients with seropositive, erosive early rheumatoid arthritis in the US, Germany, Spain, and Canada.

BACKGROUND: Effective treatment of rheumatoid arthritis (RA) with biologic DMARDs poses a significant economic burden. The AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE RA subjects with background methotrexate) trial was a head-to-head, randomized study comparing abatacept with adalimumab. A post hoc analysis showed improved efficacy for abatacept in patients with versus without seropositive, erosive early RA. OBJECTIVE: The aim of the current study was to evaluate the cost per response (ACR20/50/70/90 and HAQ-DI) and patient in remission (DAS28-CRP, CDAI, and SDAI) for abatacept relative to adalimumab, in patients with seropositive, erosive early RA in the US, Germany, Spain, and Canada. METHODS: A previously published model was used to compare abatacept and adalimumab in a cohort of 1000 patients over 2 years. Clinical inputs were updated based on two subpopulations from the AMPLE trial. Cohort 1 included patients with early RA (disease duration ≤ 6 months), RF and/or ACPA seropositivity, and > 1 radiographic erosion. Cohort 2 included patients with RA in whom at least one of these criteria was absent. RESULTS: For cohort 1, all incremental costs per additional health gain (patient response or patient in remission) favoured abatacept in all countries, except for DAS28-CRP remission in Canada. Cost savings versus adalimumab were greater when more stringent response criteria were applied and also in cohort 1 patient (versus cohort 2 patients). CONCLUSION: The cost per responder and patient in remission favoured abatacept in patients with seropositive, erosive early RA across all the countries. In this patient population, the use of abatacept instead of adalimumab can lead to lower costs in the US, Germany, Spain, and Canada.

[Survey of rheumatologists in Saxony, Saxony-Anhalt and Thuringia regarding the occupational situation and activities in further education: no way out of the undersupply of rheumatological care]. / Befragung von Rheumatologen in Sachsen, Sachsen-Anhalt und Thüringen zu Weiterbildungstätigkeit und beruflicher Situation: Kein Ausweg aus der rheumatologischen Unterversorgung.

INTRODUCTION: Many regions in the middle of Germany have a deficit in specialized rheumatological care. A survey was undertaken to investigate whether the regional capacities for rheumatological advanced training are sufficient to provide an adequate number of rheumatologists in the future. METHODS: All 91 rheumatologists registered in Saxony, Saxony-Anhalt and Thuringia received a questionnaire that was sent back by 66% of the recipients (23 responses from Saxony, 19 from Saxony-Anhalt, 18 from Thuringia). Of the rheumatologists 41 were in private practice, 19 worked in an inpatient department and the mean duration of professional activity was 18 years. RESULTS: Over the last decade the number of patients treated by rheumatologists in private practices increased from 1200 to 1500 per quarter year (p < 0.001), whereas the number of first consultations rose from 100 to 130 per quarter year (p = 0.06). The waiting time for a first consultation rose from 8 to 11 weeks (p = 0.01), 32% of the responders indicated that the conditions for outpatient treatment had either improved or had remained constant during the last 10 years, whereas 60% reported a mild or marked deterioration and 48% stated that the number of rheumatologists had decreased within the same time frame. Only 20% indicated that they had a definite successor in the practice after retirement. All inpatient departments also had an outpatient office. During the last 10 years, the number of consultations per quarter year decreased from 1100 to 700 (not significant), while the waiting time doubled from 6 to 12 weeks (rounded mean). Of the rheumatologists in private practice eight are currently entitled to provide advanced education in rheumatology, with a median training period of 18 months; however, none of the responding physicians had actually brought assistant doctors to the final examination during the last decade and only one prospective rheumatologist was currently completing training in a private practice setting. Only 6 out of 12 inpatient rheumatological facilities are entitled to educate rheumatologists over the whole training period, 5 facilities were not involved in training at all and 7 indicated that they lacked applications for rheumatology training. During the last 10 years, 37 rheumatologists completed the training of which 18 went into private practice, 8 worked as general practitioners and 29 remained in the region of their initial training. CONCLUSION: Given the increase in the number of outpatients served, the volume of training activities in rheumatology is hardly sufficient to improve the deficit of rheumatological care in the middle of Germany.

Cost-effectiveness of early treatment of ACPA-positive rheumatoid arthritis patients with abatacept.

OBJECTIVES: Studies have reported that the presence of elevated anti-citrullinated protein antibodies (ACPA)/RF levels, together with joint erosions, is associated with higher disease burden in terms of disability and mortality in rheumatoid arthritis (RA). Abatacept has been shown to be effective in this patient population with favourable comparative data against adalimumab. However, few studies have investigated the cost-effectiveness of abatacept in this population to similar treatments such as TNFs. The objective of the study was to compare the cost-effectiveness of abatacept to adalimumab as a first bDMARD in ACPA-positive RA patients who failed treatment with methotrexate (MTX) in Germany. METHODS: A decision tree model was used to estimate the cost-effectiveness, from a payer's perspective, of different treatment sequences in RA over a two year time frame. The effectiveness criteria were defined as achieving the treatment target measured by the Disease Activity Score 28 (DAS28(CRP)<2.6; "remission"). A treatment switch to a different biologic as 2nd line and 3rd line bDMARD was allowed - in case of not achieving remission with therapy - every 6 months over a two year time period. Effectiveness data was based on randomised controlled trials (RCT) identified by an updated previous systematic literature search by the Institute for Quality and Efficiency in Health Care (IQWiG). Costs of medication and other direct medical costs were considered. Cost-effectiveness of RA treatment was investigated in ACPA-positive patients and presented as overall costs per day in remission. RESULTS: For ACPA-positive patients, treatment strategies including early treatment with abatacept had lower total costs per clinical outcome compared to later use. Treatment sequences starting with abatacept resulted in lower costs per day in remission (mean 330 €/day, range 328-333 €/day) compared to sequences starting with adalimumab (mean 384 €/day, range 378-390 €/day). Choice of the second or third biologic in the treatment sequences appears to have little impact on the costs per outcome. CONCLUSIONS: The results of this analysis suggest that in ACPA-positive RA patients treatment with abatacept appears to have lower costs per response (remission) compared to treatment with adalimumab as a first bDMARD.

Cost per response for abatacept versus adalimumab in rheumatoid arthritis by ACPA subgroups in Germany, Italy, Spain, US and Canada.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada. A cost-consequence analysis (CCA) was designed to compare the monthly costs per responding patient/patient in remission. Efficacy, safety and resource use inputs were based on the AMPLE trial. A one-way deterministic sensitivity analysis (OWSA) was also performed to assess the impact of model inputs on the results for total incremental costs. Cost per response in ACPA-positive patients favoured abatacept compared with adalimumab (ACR20, ACR90 and HAQ-DI). Subgroup analysis favoured abatacept with increasing stringency of response criteria and serum ACPA levels. Cost per remission (DAS28-CRP) favoured abatacept in ACPA-negative patients, while cost per CDAI and SDAI favoured abatacept in ACPA-positive patients. Abatacept was consistently favoured in ACPA-Q4 patients across all outcomes and countries. Cost savings were greater with abatacept when more stringent response criteria were applied and also with increasing ACPA levels, which could lead to a lower overall health care budget impact with abatacept compared with adalimumab.

Cost-effectiveness simulation model of biologic strategies for treating to target rheumatoid arthritis in Germany.

OBJECTIVES: The treatment of active rheumatoid arthritis (RA) usually requires different therapeutic options used sequentially in case of an insufficient response (IR) to previous agents. Since there is a lack of clinical trials comparing biologic treatment sequences, simulation models might add to the understanding of optimal treatment sequences and their cost-effectiveness. The objective of this study was to assess the cost-effectiveness of different biologic treatment strategies in patients with an IR to anti-TNF agents, based on levels of disease activity from the German public payer's perspective. METHODS: A cost-effectiveness sequential model was developed in accordance with local RA treatment strategies, using DAS28 scores as dichotomous effectiveness endpoints: achieving remission/no remission (RS/no RS) or a state of low disease activity (LDAS/no LDAS). Costs were estimated using resource utilisation data obtained from a large observational German cohort. Advanced simulations were conducted to assess the cost-effectiveness over 2 years of four sequential biologic strategies composed of up to 3 biologic agents, namely anti-TNF agents, abatacept or rituximab, in patients with moderate-to-severe active RA and an IR to at least one anti-TNF agent. RESULTS: Over two years, the biological sequence including abatacept after an IR to one anti-TNF agent appeared the most effective and cost-effective versus (vs.) use after two anti-TNF agents (€633 vs. €1,067/day in LDAS and €1,222 vs. €3,592/day in remission), and vs a similar sequence using rituximab (€633 vs. €728/day in LDAS and €1,222 vs. €1,812/day in remission). The sequence using a 3rd anti-TNF agent was less effective and cost-effective than the same sequence using abatacept (€2,000 vs. €1,067/day in LDAS and €6,623 vs. €3,592/day in remission). All differences were statistically significant (p<0.01). CONCLUSIONS: The results suggest that in patients with an IR to at least one anti-TNF agent, biologic sequences including abatacept appear more efficacious and cost-effective than similar sequences including rituximab or only cycled anti-TNF agents.