Publications

What is a Publication?
100 Publications visible to you, out of a total of 100
Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT

Abstract (Expand)

INTRODUCTION: We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis … (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs). METHODS: The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis). RESULTS: A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFalpha agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFalpha: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFalpha agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFalpha vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFalpha agents (P = 1.0). CONCLUSIONS: No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.

Authors: A. Strangfeld, F. Hierse, R. Rau, G. R. Burmester, B. Krummel-Lorenz, W. Demary, J. Listing, A. Zink

Date Published: 2010

Publication Type: Journal

Comparative effectiveness of tumour necrosis factor alpha inhibitors in combination with either methotrexate or leflunomide

Abstract (Expand)

OBJECTIVE: The objective of this study was to compare the effectiveness of a combination of tumour necrosis factor alpha (TNFalpha) inhibitors with either methotrexate or leflunomide in the treatment … of patients with rheumatoid arthritis in a real-world setting. METHODS: Data from 1769 outpatients enrolled in the German biologics register RABBIT who were treated with one of the TNFalpha inhibitors adalimumab, etanercept, or infliximab in combination with either methotrexate (n = 1375) or leflunomide (n = 394) were included in the analysis. Clinical status including disease activity as well as treatment data were documented by the treating rheumatologist at baseline and at 3, 6, 12, 18, 24, 30 and 36 months of follow-up. RESULTS: Patients treated with a combination of biologics with leflunomide had significantly higher baseline disease activity than those treated with methotrexate. The highest disease activity was found for patients treated with the combination infliximab/leflunomide. After 36 months, the discontinuation rates were 46.3%, 51.3% and 61.5% for combinations of etanercept, adalimumab and infliximab with methotrexate and 53.4%, 63.1% and 67.1% for combinations with leflunomide, respectively. European League Against Rheumatism response rates after 24 months ranged from 74% to 81% for combinations with methotrexate and 72% to 81% for combinations with leflunomide. CONCLUSION: The current clinical practice is to use methotrexate as a first choice for the combination with TNFalpha antagonists. In a number of patients methotrexate has to be replaced by another disease-modifying antirheumatic drug. Our data support the view that leflunomide is a useful alternative if methotrexate is contraindicated.

Authors: A. Strangfeld, F. Hierse, J. Kekow, U. von Hinueber, H. P. Tony, R. Dockhorn, J. Listing, A. Zink

Date Published: 2009

Publication Type: Journal

Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents

Abstract (Expand)

CONTEXT: The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor alpha (TNF-alpha). Little is known about the reactivation of latent viral infections … during treatment with TNF-alpha inhibitors. OBJECTIVE: To investigate whether TNF-alpha inhibitors together as a class, or separately as either monoclonal anti-TNF-alpha antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis. DESIGN, SETTING, AND PATIENTS: Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up. MAIN OUTCOME MEASURES: Hazard ratio (HR) of herpes zoster episodes following anti-TNF-alpha treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF-alpha inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF-alpha inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs. RESULTS: Among 5040 patients receiving TNF-alpha inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti-TNF-alpha antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.6-13.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.73-2.55]) or for anti-TNF-alpha treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class. CONCLUSION: Treatment with monoclonal anti-TNF-alpha antibodies may be associated with increased risk of herpes zoster, but this requires further study.

Authors: A. Strangfeld, J. Listing, P. Herzer, A. Liebhaber, K. Rockwitz, C. Richter, A. Zink

Date Published: 2009

Publication Type: Journal

Does tumor necrosis factor alpha inhibition promote or prevent heart failure in patients with rheumatoid arthritis?

Abstract (Expand)

OBJECTIVE: To determine the hazard risk of developing or worsening heart failure in rheumatoid arthritis (RA) patients treated with tumor necrosis factor alpha (TNFalpha) inhibitors. METHODS: RA patients … ages 18-75 years who started treatment with infliximab, etanercept, or adalimumab (n = 2,757), or conventional disease-modifying antirheumatic drugs (controls; n = 1,491) at the time of enrollment in a German biologics register were studied. Cox proportional hazards models were applied to investigate the influence of disease-related and treatment-specific risk factors on the incidence or worsening of heart failure. RESULTS: The 3-year incidence rates of heart failure in patients with and patients without cardiovascular disease at the start of treatment were 2.2% and 0.4%, respectively. After adjustment for traditional cardiovascular risk factors, an increased risk of developing heart failure was found in patients who had a higher 28-joint Disease Activity Score at followup (hazard ratio [HR] 1.47 [95% confidence interval 1.07-2.02], P = 0.019). A residual nonsignificant risk related to treatment with TNFalpha inhibitors remained (adjusted HR 1.66 [95% confidence interval 0.67-4.1], P = 0.28). This residual risk was balanced by the efficacy of the anti-TNF treatment. When only baseline characteristics were taken into account, the HR related to TNFalpha inhibitor treatment decreased to 0.70 (95% confidence interval 0.27-1.84). CONCLUSION: The findings of this study indicate that TNFalpha inhibitor treatment that effectively reduces the inflammatory activity of RA is more likely to be beneficial than harmful with regard to the risk of heart failure, especially if there is no concomitant therapy with glucocorticoids or cyclooxygenase 2 inhibitors. Furthermore, the data suggest that TNFalpha inhibition does not increase the risk of worsening of prevalent heart failure.

Authors: J. Listing, A. Strangfeld, J. Kekow, M. Schneider, A. Kapelle, S. Wassenberg, A. Zink

Date Published: 2008

Publication Type: Journal

Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low–results from RABBIT, the German biologics register

Abstract (Expand)

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of … a functional status above defined thresholds (’functional remission’, ’physical independence’) in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis–Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2-3.2)); ARA remission, OR 2.05 (95% CI 1.2-3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (< or = 50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (> or = 67% of full function) than controls (OR 3.88 (95% CI 1.7-8.8)). ’Functional remission’ (> or = 83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04-4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only.

Authors: J. Listing, A. Strangfeld, R. Rau, J. Kekow, E. Gromnica-Ihle, T. Klopsch, W. Demary, G. R. Burmester, A. Zink

Date Published: 2006

Publication Type: Journal

[Dose adjustment in patients treated with infliximab in routine rheumatologic care in Germany. Results from the Biologics Register RABBIT]

Abstract (Expand)

OBJECTIVE: Data from international observational studies show that a considerable proportion of patients use higher dosages of infliximab (INF) than the usual 3 mg every 8 weeks used in Germany for … treatment of rheumatoid arthritis. The Data are, however, inconsistent and vary between countries. Using data from the German Biologics Register RABBIT we investigated: (1) how dosage of INF develops during the first year of treatment in routine care, and (2) how dosage translates into clinical effectiveness. PATIENTS: We analysed data from 344 patients who started a treatment with INF at their inclusion into the register and who were observed for the subsequent 12 months. Mean dosage at 3 months (after the loading dose) was 3.2 mg/kg body weight/infusion and 3.3 mg/kg after 1 year. If we also consider shortening the infusion intervals, the mean dosages at the start and after 1 year were 4.0 mg/kg body weight every 8 weeks. RESULTS: Patients who were treated with low dosages of up to 3 mg/kg/8 weeks showed significantly less improvement (EULAR response) than those who were treated with higher dosages. CONCLUSIONS: The data show that German rheumatologists are aware of the high costs of treatment and try to use the lowest possible dosage. However, for a certain proportion of the patients this might be insufficient.

Authors: A. Zink, J. Listing, A. Strangfeld, E. Gromnica-Ihle, W. Demary, M. Schneider

Date Published: 2006

Publication Type: Journal

Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials

Abstract (Expand)

OBJECTIVE: Randomized clinical trials (RCTs) evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic … effectiveness in "real world" patients is limited. This observational cohort study was designed to complement the knowledge obtained in RCTs by evaluating the effectiveness of tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) according to their eligibility for the major trials. METHODS: Using the data from the German biologics register Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT [in German]), we investigated how many of the RA patients who were treated with a TNF inhibitor (infliximab, etanercept, or adalimumab) would have been eligible for the major clinical trials that led to approval of the drugs. In addition, therapeutic effectiveness was compared in the eligible and ineligible patients using the American College of Rheumatology 20% (ACR20) and 50% (ACR50) improvement response criteria. RESULTS: Only 21-33% of the patients in the RABBIT register would have been eligible for the major trials. In these patients, the ACR20 and ACR50 improvement responses, indicating therapeutic effectiveness, were comparable with the response rates in the published trials. ACR response rates were lower in those patients considered ineligible for the trials; however, absolute improvement was similar to that in eligible patients. Ineligible patients had lower baseline disease activity, more comorbidity, and lower functional status. CONCLUSION: RCT cohorts reflect only a minor proportion of the patients treated with biologic agents in routine care. In the clinic setting, the indications for treatment with biologic agents are not identical to the inclusion criteria for trials. Despite the smaller relative improvement achieved in these patients with longstanding, severe RA who would not fulfill the inclusion criteria of a major trial, the majority of such patients would nevertheless benefit from biologic therapy.

Authors: A. Zink, A. Strangfeld, M. Schneider, P. Herzer, F. Hierse, M. Stoyanova-Scholz, S. Wassenberg, A. Kapelle, J. Listing

Date Published: 2006

Publication Type: Journal

Powered by
 (v.1.17.3)

(LDH: v0.3.4)

About NFDI4Health | About Local Data Hub DRFZ Berlin | Partners and Funding | Credits | Terms & Conditions | Privacy Policy | Imprint
Copyright © 2008 - 2023 The University of Manchester and HITS gGmbH
Additions copyright ...