Publications

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216 Publications visible to you, out of a total of 216
Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient?

Abstract (Expand)

OBJECTIVE: To examine the risk of serious infection conveyed by tumour necrosis factor alpha (TNFalpha) inhibitors in the treatment of rheumatoid arthritis (RA). METHODS: Data from patients with RA … enrolled in the German biologics register RABBIT were used for analysis. Baseline patient characteristics, time-varying risk factors (treatment changes, functional capacity) and selection processes caused by dropout, death or switching to non-anti-TNF treatment were taken into account to estimate the adjusted incidence rate ratios (IRR(adj)) of serious infection during treatment with TNF inhibitors compared with non-biological disease-modifying antirheumatic drug treatment. RESULTS: Data were available on 5044 patients, in whom 392 serious infections occurred. The crude rates of serious infections in patients treated with TNF inhibitors declined over the first 3 years of observation (from 4.8 to 2.2/100 patient-years). This decline was driven by (1) treatment termination or loss to follow-up in patients at increased risk and (2) a risk reduction through decreasing glucocorticoid doses and improvement in function. Adjusted for selection processes and time-varying risk factors, the following parameters assessed at baseline (age, chronic diseases) or at follow-up prior to the infection were significantly associated with an increased risk: age >60 years, chronic lung or renal disease, low functional capacity, history of serious infections, treatment with glucocorticoids (7.5-14 mg/day, IRR(adj) 2.1 (95% CI 1.4 to 3.2); >/= 15 mg/day, IRR(adj) 4.7 (95% CI 2.4 to 9.4)) and treatment with TNFalpha inhibitors (IRR(adj) 1.8 (95% CI 1.2 to 2.7)). CONCLUSION: Reasons for the decline in infection rates observed at the group level were identified. The results enable expected infection rates to be calculated in individual patients based on their risk profiles.

Authors: A. Strangfeld, M. Eveslage, M. Schneider, H. J. Bergerhausen, T. Klopsch, A. Zink, J. Listing

Date Published: 2011

Publication Type: Journal

Detection and evaluation of a drug safety signal concerning pancreatic cancer: lessons from a joint approach of three European biologics registers

Abstract (Expand)

OBJECTIVES: A high incidence of pancreatic cancer (PCa) in patients exposed to was observed in the German biologics register. To evaluate this possible safety signal, a concerted analysis with the … national biologics registers in the UK and Sweden was performed. METHODS: Patients with enrolled in the British Society of Rheumatology Biologics Register (BSRBR), the Swedish Rheumatology Register (SRR) or the German Biologics Register [Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT)] were analysed. The patients were exposed to biologic or conventional DMARDs. Outcomes were obtained from physician reports, health authorities and via linkage to national cancer and death registers. Age- and gender-standardized incidence ratios (SIRs) of PCa were calculated based on the expected rates available from the individual national cancer registers. RESULTS: Data from 5126 (Germany), 16 930 (UK) and 19 351 (Sweden) RA patients were available for the analysis. The highly discrepant prescription rates of LEF in the respective countries resulted in 11 343 (Germany), 30 787 (UK) and 2518 (S) patient-years of exposure to LEF. Compared with the general population, the incidence of PCa in patients ever exposed to LEF corresponded to a SIR of 3.1 (95% CI 1.3, 6.5) in Germany, 1.05 (95% CI 0.5, 2.1) in the UK and 1.8 (95% CI 0.1, 10.2) in Sweden. CONCLUSION: The results of the replication analyses do not support the hypothesis of an increased risk of PCa in patients exposed to treatment with LEF. However, they do not completely rule out concerns, and therefore further verification in other data sets is recommended.

Authors: A. Strangfeld, K. Hyrich, J. Askling, E. Arkema, R. Davies, J. Listing, M. Neovius, J. Simard, D. Symmons, K. Watson, A. Zink

Date Published: 2011

Publication Type: Journal

Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl antibody

Abstract (Expand)

BACKGROUND: To date, no series has analysed long-term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody. OBJECTIVES: The aims of the present study were: (i) to … assess clinical features and long-term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate prevalence, characteristics and long-term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody. METHODS: The medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl antibody were reviewed. RESULTS: Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short-term recurrences (during tapering of therapy) occurred in nine patients and long-term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti-PM-Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud’s phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents. CONCLUSIONS: Our series suggests that the presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive patients with PM/DM often exhibit ’mechanic’s hands’, Raynaud’s phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA-DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti-PM-Scl antibodies.

Authors: I. Marie, L. Lahaxe, O. Benveniste, K. Delavigne, D. Adoue, L. Mouthon, E. Hachulla, J. Constans, K. Tiev, E. Diot, H. Levesque, O. Boyer, F. Jouen

Date Published: 2010

Publication Type: Journal

[Epidemiology of primary Sjorgren’s syndrome]

Abstract (Expand)

According to the classification criteria of the American-European Consensus Group (AECG), the prevalence of primary Sjogren’s syndrome (pSS) of about 0.2% in the adult population and a yearly incidence … of 4/100.000 in the general population are far lower than previously assumed. Moreover, the repeatedly reported male/female ratio of 1:9 seems to lie more in the range of 1:20. Male pSS patients show fewer immunological, histopathological or sialographic findings and organ involvement. Information on age at disease onset has also changed over the last decade. Recent studies indicate an onset age of approximately 45 years as compared to 56 in earlier studies of the last decade. Patients with an early disease onset are more frequently positive for rheumatoid factor (RF) and/or anti-Ro/SS-A. These patients also seem to have a higher risk of developing hypocomplementemia or lymphadenopathy. As compared to earlier cohorts, the introduction of the rather specific AECG criteria will probably result in the participation of fewer men, younger patients in general and of more seriously ill patients in future cohorts. The change in the spectrum of pSS patients obviously reflects the altered classification criteria since the AECG criteria require anti-Ro/La positivity and therefore exclude a high number of patients with other immunological markers who also show severe sicca symptoms and organ involvements. About 5%-10% of pSS patients in rheumatological care suffer from severe extraglandular manifestations, which generally occur soon after disease onset. In particular, palpable purpura, hypocomplementemia, cryoglobulinemia and lymphoma are associated with increased mortality. In Germany, approximately one tenth of Sjogren syndrome patients receive specialized rheumatological care. There is still insufficient knowledge about the vast majority of pSS patients who are not treated by rheumatologists. These patients, as well as all those who, according to the AECG criteria, are not classified as having pSS either due to anti-Ro/La negativity or having secondary Sjogren’s syndrome, probably add up to at least 0.4% of the adult population which, at present, suffers from considerable immunopathologic sicca symptoms.

Authors: G. Westhoff, A. Zink

Date Published: 2010

Publication Type: Journal

Trends in treatment and outcomes of rheumatoid arthritis in Germany 1997-2007: results from the National Database of the German Collaborative Arthritis Centres

Abstract (Expand)

BACKGROUND: New strategies and options for the treatment of rheumatoid arthritis (RA) have evolved during the past decade. A study was undertaken to investigate to what extent this influenced daily … rheumatological care and how this translates into clinical and patient-reported outcomes. METHODS: Data from a total of 38 723 outpatients with RA enrolled in the National Database of the German Collaborative Arthritis Centres in the years 1997-2007 were analysed. The cross-sectional annual data were compared to detect time trends. RESULTS: Between 1997 and 2007 the prescription of combinations of traditional disease-modifying antirheumatic drugs (DMARDs) increased from 8% of all patients to 23%; biological agents were prescribed to 16% of patients with RA in 2007. The mean disease activity (DAS28) fell from 4.5 to 3.4 (median 4.5-3.2). The percentage of patients with low disease activity (DAS28 <3.2) increased significantly from 23% to 49%. The proportion of patients with >/=6 swollen joints fell from 43.1% in 1997 to 8.1% in 2007 and, in those with >/=6 tender joints, from 46.3% to 15.8%. There was a large decrease in the total annual number of days of sick leave due to the rheumatic condition from 27.2 to 8.8 days per gainfully employed person. This reduction is far beyond the decline in the general population. There was also a tendency to higher participation in the work force, specifically in older patients, reflecting the trend seen in the general population. CONCLUSIONS: The intensity of drug treatment in patients with RA has increased during the past 7 years. This has been accompanied by not only a decrease in disease activity but also a considerable reduction of economic losses due to sick leave and permanent work disability.

Authors: S. Ziegler, D. Huscher, K. Karberg, A. Krause, S. Wassenberg, A. Zink

Date Published: 2010

Publication Type: Journal

[How closely does rheumatology treatment follow the guidelines?: ambition and reality]

Abstract (Expand)

In 2005, the first evidence-based German guideline on the management of early rheumatoid arthritis (RA) was published. With data from the national database of the German Collaborative Arthritis Centres … and other health care studies we evaluated to what extent current health care is in accordance with the guideline’s recommendations.A total of 66% of all newly referred RA patients seen at the national database centers in 2008 achieved the goal of seeing a rheumatologist within 3 months of symptom onset, while 75% were seen within 6 months. Before referral, 25% of the patients had DMARD therapy and 19% glucocorticoids. Of the patients in rheumatological care, 90% received DMARDs. The availability of early arthritis clinics determines the promptness of access to a rheumatologist.After 6 years of rheumatological care, around 80% of patients continuously seen were still under treatment with a conventional or biological DMARD. The highest continuation rates were seen for methotrexate monotherapy. Biologic agents were given in 2008 to 20% of patients. Of those with "severe" or "very severe" disease, 42% received biologics and 21% DMARD combination therapy. Low-dose glucocorticoids are the standard of care; of patients in rheumatological care, 88% received dosages up to 7.5 mg/d and 74% of up to 5 mg/d.

Authors: A. Zink, D. Huscher, M. Schneider

Date Published: 2010

Publication Type: Journal

[The importance of patient perspective in drug surveillance systems]

Abstract (Expand)

AIMS: using data from the German biologics register RABBIT we investigated which gain in information can be achieved by integrating patient-reported adverse drug reactions (ADRs) into drug surveillance … systems. METHODS: patients with rheumatoid arthritis enrolled in the longitudinal cohort of the German biologics register between May 2001 and September 2006 who had undergone at least one follow-up were included in the study. All ADRs reported to the register either by the treating rheumatologists or the patients were coded with the same coding system (MedDRA(R)). The agreement between patients and physicians was analysed for the most frequently reported ADRs using the patient as gold standard. RESULTS: data from 4246 patients with a mean observation time of 2 years were analysed. Patients reported on average 1.2 ADRs per patient year (PY), while physicians indicated 1 ADR per PY (p<0,001). The ADR most frequently reported by patients was nausea (93.8 per 1000 PY), followed by fatigue (72.5 per 1000 PYs) and alopecia (60.6 per 1000 PYs). These ADRs were significantly less often reported by physicians. Agreement between patients and physicians was higher in more objective symptoms, such as injection site reaction (in 60.0% of cases where the patient reported this symptom, the physician did so too) or rash (53.0%), than in more subjective symptoms such as fatigue (17.4%). Agreement was highest in life-threatening events. CONCLUSIONS: patients report a higher number of ADRs than their treating physicians. Patients report subjective symptoms impacting on quality of life more frequently than physicians. Patient-physician agreement on known or clinically relevant ARDs is high. Integration of patient reports on ADRs into clinical routine could enhance the patient-physician partnership and improve compliance as well as awareness of signs and symptoms of possible ADRs.

Authors: L. Gawert, F. Hierse, A. Zink, A. Strangfeld

Date Published: 2010

Publication Type: Journal

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