Publications

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100 Publications visible to you, out of a total of 100
Long-term effectiveness of tocilizumab in patients with rheumatoid arthritis, stratified by number of previous treatment failures with biologic agents: results from the German RABBIT cohort

Abstract (Expand)

In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naive patients and those with previous failures of biologic disease-modifying antirheumatic drugs … (bDMARDs). The long-term effectiveness and retention rates of TCZ in patients with different numbers of prior bDMARD failures has rarely been investigated. We included 885 RA patients in the analyses, enrolled with the start of TCZ between 2009 and 2015 in the German biologics register RABBIT. Patients were stratified according to prior bDMARD failures: no prior bDMARD or 1, 2 or >/= 3 bDMARD failures. We applied Kaplan-Meier methods and Cox-regression to examine treatment adherence as well as linear mixed effects models to investigate effectiveness over 3 years of follow-up. Compared to biologic-naive patients, those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration and more comorbidities. DAS28 at baseline and loss of physical function were highest in patients with >/= 3 bDMARD failures. During follow-up, patients with up to two bDMARD failures on average reached low disease activity (LDA, DAS28 < 3.2). Those with >/= 3 prior bDMARDs had a slightly lower response. However, after 3 years, nearly 50% of them achieved LDA. Treatment continuation on TCZ therapy was similar in patients with </= 2 bDMARD failures but significantly lower in those with >/= 3 bDMARD failures. TCZ seems to be similarly effective in patients with no, one or two prior bDMARD failures. The majority of patients achieved LDA already after 6 months and maintained it over a period of 3 years. TCZ proved effective even in the high-risk group of patients with more than two prior bDMARD failures.

Authors: L. Baganz, A. Richter, J. Kekow, A. Bussmann, A. Krause, C. Stille, J. Listing, A. Zink, A. Strangfeld

Date Published: 2018

Publication Type: Journal

[Revised version of the statement by the DGRh on biosimilars-update 2017]

Abstract (Expand)

The treatment of rheumatic diseases with bioloics has significantly improved the prognosis of patients. Currently, there are 13 preparations available in Germany for the treatment of patients with … inflammatory rheumatic diseases. These original preparations generally have-depending on the individual country-15 years of patent protection. As soon as the patent has expired, approved biosimilars can be brought into use. For the approval of a biosimilar, authorities such as the European Medical Agency or the American Food and Drug Administration require proof of the best possible comparability with respect to efficacy and safety in comparison to the original or reference product. Since 2015, biosimilars of inifliximab, adalimumab, etanercept and rituximab have been granted approval in the European Union, the USA, Japan and in other countries. Further biosimilar products for these reference products are in development for treatment in rheumatology. From a societal and medical point of view, this opens up the possibility to increase the availability of biopharmaceutical products for patients through lower prices. In Germany, this possibility has already occurred-statutory health insurance physicians have introduced quotas for biosimilars, which will ultimately decrease spending and healthcare costs. This can lead to price reductions of the original products, which has already happened in Germany. Biosimilars can be prescribed for new patients or as a change from the original to the generic drug. When switching, a distinction is made between individual switching (interchangeability), which is made in individual consultation between the physician and the patient, and nonmedical switching (substitution) made at the societal or governmental level, which is made in the context of health care cost containment, and then, for example, implemented at the pharmacy level. Preliminary data from Norway and Denmark are available for substitution on the basis of results from large studies or registries in which systematic changes were made. The previous conclusion was that this does not lead to new problems for the patients. The German Society for Rheumatology recognizes the advantages of introducing biosimilars in Germany, but recommends that their use be based primarily on a joint decision by the treating physician and patient.

Authors: J. Braun, H. M. Lorenz, U. Muller-Ladner, M. Schneider, H. Schulze-Koops, C. Specker, A. Strangfeld, U. Wagner, T. Dorner

Date Published: 2018

Publication Type: Journal

Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases

Abstract (Expand)

The study aimed to develop evidence-based recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases. The task force comprised an expert group of specialists in … rheumatology, dermatology and gastroenterology, and pharmacologists, patients and a regulator from ten countries. Four key topics regarding biosimilars were identified through a process of discussion and consensus. Using a Delphi process, specific questions were then formulated to guide a systematic literature review. Relevant English-language publications through November 2016 were searched systematically for each topic using Medline; selected papers and pertinent reviews were examined for additional relevant references; and abstracts presented at the 2015 and 2016 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) annual scientific meetings were searched for those about biosimilars. The experts used evidence obtained from these studies to develop a set of overarching principles and consensus recommendations. The level of evidence and grade of recommendation were determined for each. By the search strategy, 490 references were identified. Of these, 29 full-text papers were included in the systematic review. Additionally, 20 abstracts were retrieved from the ACR and EULAR conference abstract databases. Five overarching principles and eight consensus recommendations were generated, encompassing considerations regarding clinical trials, immunogenicity, extrapolation of indications, switching between bio-originators and biosimilars and among biosimilars, and cost. The level of evidence and grade of recommendation for each varied according to available published evidence. Five overarching principles and eight consensus recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases were developed using research-based evidence and expert opinion.

Authors: J. Kay, M. M. Schoels, T. Dorner, P. Emery, T. K. Kvien, J. S. Smolen, F. C. Breedveld, Diseases Task Force on the Use of Biosimilars to Treat Rheumatological

Date Published: 2018

Publication Type: Journal

[How frequent are poor prognostic markers in rheumatoid arthritis? : An estimate based on three epidemiologic cohorts]

Abstract (Expand)

BACKGROUND: Unfavorable prognostic factors-high disease activity, early erosions, and autoantibodies-should be considered when making treatment decisions in rheumatoid arthritis (RA). There are little … data on the frequency of individual poor prognostic factors among RA patients in daily care. METHODS: Disease activity (Disease Activity Score, DAS28), erosions, antibodies against citrullinated peptides or rheumatoid factor (ACPA/RF+), previous treatment failure, inflammation markers, and functional disability (FFbH < 70) were defined as prognostic factors. Different treatment decision making situations were evaluated in disease-modifying antirheumatic drug (DMARD)-naive patients from the early RA CAPEA cohort (n = 1059), and in patients from the biologics register RABBIT after failure of one (n = 2217) or more (n = 3280) conventional synthetic (cs)DMARDs or one (n = 1134) or more (n = 795) biologic (b)DMARDs. With the national database of German arthritis centers (NDB), the frequency of these factors was analyzed according to treatment strata (no/1(st)/2(nd)/3(rd) DMARD; n = 5707). RESULTS: In DMARD-naive patients (CAPEA), 50% presented with DAS28 > 5.1, 64% were ACPA/RF+, 13% had erosions, and 37% functional disability (FFbH < 70). In RABBIT, 63 (1(st) csDMARD failure) to 81% (>/=2 bDMARD failures) were ACPA/RF+, 29 to 70% had erosions, 33 to 52% DAS28 > 5.1, and 41 to 66% had FFbH < 70, respectively. In the NDB, between 47 (DMARD-naive) and 82% (>/=2 previous DMARDs) were ACPA/RF+, 5 to 11%, had high disease activity under treatment (DAS28 > 5.1), and 26 to 50% had functional disability (FFbH < 70), respectively. CONCLUSION: With growing numbers of previous DMARD therapies, increasing proportions of patients have poor prognostic factors. This underlines the importance of these factors for a difficult-to-treat disease course.

Authors: K. Albrecht, A. Richter, Y. Meissner, D. Huscher, L. Baganz, K. Thiele, M. Schneider, A. Strangfeld, A. Zink

Date Published: 2017

Publication Type: Journal

Serious adverse events and the risk of stroke in patients with rheumatoid arthritis: results from the German RABBIT cohort

Abstract (Expand)

OBJECTIVE: In the general population, the incidence of stroke is increased following other serious events and hospitalisation. We investigated the impact of serious adverse events on the risk of stroke … in patients with rheumatoid arthritis (RA), taking risk factors and treatment into account. METHODS: Using data of the German biologics register RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) with 12354 patients with RA, incidence rates (IRs) and risk factors for stroke were investigated using multi-state and Cox proportional hazard models. In addition, in a nested case-control study, all patients with stroke were matched 1:2 to patients with identical baseline risk profile and analysed using a shared frailty model. RESULTS: During follow-up, 166 strokes were reported. The overall IR was 3.2/1000 patient-years (PY) (95% CI 2.7 to 3.7). It was higher after a serious adverse event (IR: 9.0 (7.3 to 11.0)), particularly within 30 days after the event (IR: 94.9 (72.6 to 121.9)). The adjusted Cox model showed increased risks of age per 5 years (HR: 1.4 (1.3 to 1.5)), hyperlipoproteinaemia (HR: 1.6 (1.0 to 2.5)) and smoking (HR: 1.9 (1.3 to 2.6)). The risk decreased with better physical function (HR: 0.9 (0.8 to 0.96)). In the case-control study, 163 patients were matched to 326 controls. Major risk factors for stroke were untreated cardiovascular disease (HR: 3.3 (1.5 to 7.2)) and serious infections (HR:4.4 (1.6 to 12.5)) or other serious adverse events (HR: 2.6 (1.4 to 4.8)). CONCLUSIONS: Incident adverse events, in particular serious infections, and insufficient treatment of cardiovascular diseases are independent drivers of the risk of stroke. Physicians should be aware that patients who experience a serious event are at increased risk of subsequent stroke.

Authors: Y. Meissner, A. Richter, B. Manger, H. P. Tony, E. Wilden, J. Listing, A. Zink, A. Strangfeld

Date Published: 2017

Publication Type: Journal

Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers

Abstract (Expand)

OBJECTIVES: Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the … incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naive were calculated across countries by taking the size of the register into account. RESULTS: Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naive, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naive patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9). CONCLUSIONS: This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi.

Authors: L. K. Mercer, J. Askling, P. Raaschou, W. G. Dixon, L. Dreyer, M. L. Hetland, A. Strangfeld, A. Zink, X. Mariette, A. Finckh, H. Canhao, F. Iannone, J. Zavada, J. Morel, J. E. Gottenberg, K. L. Hyrich, J. Listing

Date Published: 2017

Publication Type: Journal

Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

Abstract (Expand)

BACKGROUND: Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma … (HL) and non-Hodgkin’s lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes. METHODS: Patients never exposed to (bionaive) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD. RESULTS: Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaive patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population. CONCLUSION: This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaive patients.

Authors: L. K. Mercer, A. C. Regierer, X. Mariette, W. G. Dixon, E. Baecklund, K. Hellgren, L. Dreyer, M. L. Hetland, R. Cordtz, K. Hyrich, A. Strangfeld, A. Zink, H. Canhao, M. V. Hernandez, F. Tubach, J. E. Gottenberg, J. Morel, J. Zavada, F. Iannone, J. Askling, J. Listing

Date Published: 2017

Publication Type: Journal

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