M. Niewerth

The national database of the German Collaborative Arthritis Centres: II. Treatment of patients with rheumatoid arthritis

OBJECTIVE To describe current treatment of patients with rheumatoid arthritis (RA) in German rheumatology. METHODS Data from the German rheumatological database of 1998, comprising clinical and patient questionnaire data of 12 992 outpatients with RA seen at 24 collaborative arthritis centres in Germany, were analysed. RESULTS At the time of documentation, 88% of the patients with RA were undergoing disease modifying antirheumatic drug (DMARD) treatment. Methotrexate (MTX) was prescribed to 56% of the patients (61% with seropositive and 45% with seronegative RA). Combination treatment was used in 15%. MTX was the drug of first choice even in patients with up to one years disease duration (49%), followed by antimalarial drugs (21%). Patients treated by non-rheumatologists within the previous year had received DMARD treatment in only 33% of the cases. In steroid treatment, low doses (⩽7.5 mg/day) were used by rheumatologists much more often (44%) than higher doses (12%). 16% of the patients had been inpatients during the previous year, with a median length of stay accumulated over the year of 21 days. Together with stays in inpatient rehabilitation, 22% of all patients had had some form of inpatient treatment. Comprehensive measures such as occupational therapy and patient education were prescribed to fewer than 12% of the patients, mostly during their hospital stay. CONCLUSION German rheumatologists do follow recent recommendations about early and effective treatment. However, there are still deficits in outpatient care with non-medicinal measures like occupational therapy and patient education, which may partly explain the high hospital admission rates.

Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA)

Importance Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. Objectives To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. Design, setting and participants Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. Main outcomes and measures We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). Results Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). Conclusions and relevance Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort.

Impfungen bei rheumatischen Erkrankungen des Kindes- und Jugendalters

ZusammenfassungImpfungen stellen bei Kindern und Jugendlichen mit rheumatischen Erkrankungen ein besonderes Problem dar. Wirkungen und Nebenwirkungen von Impfungen sind für dieses Patientenkollektiv leider nur unzureichend untersucht, und spezifische Impfempfehlungen fehlen. Die bei diesen Patienten häufig erforderliche immunsuppressive Therapie schafft zusätzliche Unsicherheit. Hinzu kommen Bedenken bezüglich impfassoziierter Reaktivierungen der Grunderkrankung. Die bestehenden Unsicherheiten im Umgang mit Impfungen führen zu einer erheblichen Praxisvariation unter den Kinderärzten und Impflücken bei den betroffenen Kindern und Jugendlichen. So ist jeder dritte Patient mit juveniler idiopathischer Arthritis unzureichend geimpft, was sogar Standardimpfungen mit Totimpfstoffen wie Tetanus/Diphtherie einschließt. Nach aktuellem Stand des Wissens ist der Nutzen vieler Impfungen gerade bei Patienten mit Autoimmunerkrankungen deutlich höher als deren Risiko zu veranschlagen. Gerade Patienten mit immunsuppressiver Therapie benötigen einen besonderen Schutz vor Infektionen. Kinder und Jugendliche mit rheumatischen Erkrankungen sollten deshalb – soweit möglich – nach den STIKO-Empfehlungen geimpft werden. Dabei muss der Zeitpunkt der anstehenden Impfung sorgfältig in Abhängigkeit von der Krankheitsaktivität und Therapie gewählt werden.AbstractVaccinations represent a special problem in children and adolescents with inflammatory rheumatic diseases. There are very limited data on the safety and efficacy of vaccines in these patients, and guidelines for immunization are missing. The immunosuppressive therapy often necessary for these patients gives rise to additional uncertainty. In addition, many colleagues consider vaccination to increase the risk of relapse of the rheumatic illness. As a consequence, there are substantial variations in practicing vaccination in these patients, resulting in insufficient vaccination coverage rates. For example, every third patient with juvenile idiopathic arthritis is incompletely vaccinated; this even includes toxoid vaccines for tetanus and diphtheria. The benefit of vaccinations, which far outweighs their potential risks, is well recognized even in patients with autoimmune diseases. These patients in particular require a special protection from infections due to their immunosuppressive therapies. Therefore, children and adolescents with rheumatic diseases should be immunized according to the Standing Immunization Commission of the Robert Koch Institute recommendations whenever possible. However, the time of vaccination must be carefully selected, taking disease activity and treatment into account.

Immunization in children and adolescents with rheumatic diseases

ZusammenfassungImpfungen stellen bei Kindern und Jugendlichen mit rheumatischen Erkrankungen ein besonderes Problem dar. Wirkungen und Nebenwirkungen von Impfungen sind für dieses Patientenkollektiv leider nur unzureichend untersucht, und spezifische Impfempfehlungen fehlen. Die bei diesen Patienten häufig erforderliche immunsuppressive Therapie schafft zusätzliche Unsicherheit. Hinzu kommen Bedenken bezüglich impfassoziierter Reaktivierungen der Grunderkrankung. Die bestehenden Unsicherheiten im Umgang mit Impfungen führen zu einer erheblichen Praxisvariation unter den Kinderärzten und Impflücken bei den betroffenen Kindern und Jugendlichen. So ist jeder dritte Patient mit juveniler idiopathischer Arthritis unzureichend geimpft, was sogar Standardimpfungen mit Totimpfstoffen wie Tetanus/Diphtherie einschließt. Nach aktuellem Stand des Wissens ist der Nutzen vieler Impfungen gerade bei Patienten mit Autoimmunerkrankungen deutlich höher als deren Risiko zu veranschlagen. Gerade Patienten mit immunsuppressiver Therapie benötigen einen besonderen Schutz vor Infektionen. Kinder und Jugendliche mit rheumatischen Erkrankungen sollten deshalb – soweit möglich – nach den STIKO-Empfehlungen geimpft werden. Dabei muss der Zeitpunkt der anstehenden Impfung sorgfältig in Abhängigkeit von der Krankheitsaktivität und Therapie gewählt werden.AbstractVaccinations represent a special problem in children and adolescents with inflammatory rheumatic diseases. There are very limited data on the safety and efficacy of vaccines in these patients, and guidelines for immunization are missing. The immunosuppressive therapy often necessary for these patients gives rise to additional uncertainty. In addition, many colleagues consider vaccination to increase the risk of relapse of the rheumatic illness. As a consequence, there are substantial variations in practicing vaccination in these patients, resulting in insufficient vaccination coverage rates. For example, every third patient with juvenile idiopathic arthritis is incompletely vaccinated; this even includes toxoid vaccines for tetanus and diphtheria. The benefit of vaccinations, which far outweighs their potential risks, is well recognized even in patients with autoimmune diseases. These patients in particular require a special protection from infections due to their immunosuppressive therapies. Therefore, children and adolescents with rheumatic diseases should be immunized according to the Standing Immunization Commission of the Robert Koch Institute recommendations whenever possible. However, the time of vaccination must be carefully selected, taking disease activity and treatment into account.

The majority of newly diagnosed patients with juvenile idiopathic arthritis reach an inactive disease state within the first year of specialised care: data from a German inception cohort

Objective To describe the disease characteristics of patients with juvenile idiopathic arthritis (JIA) included in an inception cohort, to analyse how many patients from each JIA category reach an inactive disease state within the first year of specialised care and to determine predictors for attaining inactive disease. Methods Patients with JIA were enrolled in this study at 11 large German paediatric rheumatology units within the first 12 months after diagnosis. Laboratory and clinical parameters such as JIA core criteria and data on the medication used were collected every 3 months. Non-parametric statistical testing was performed for the comparison of the JIA core criteria at follow-up. Generalised linear models were used to analyse differences in the rates at which inactive disease was reached and to determine potential predictors. Results Of the 695 patients with JIA included in this analysis, approximately 75% experienced a period of inactive disease under treatment with disease-modifying antirheumatic drugs and systemic steroids in most cases with systemic-onset JIA or polyarthritis at least once during the first 12 months in ICON. Significant improvements were observed in all JIA core criteria, in disease activity and in functional status from baseline to the 12-month follow-up. Younger age at onset, a shorter duration between symptom onset and diagnosis and a positive antinuclear antibody status increased the probability of attaining an inactive disease state. Conclusions The 12-month outcome of JIA was good under real-life conditions, with half of the patients having attained inactive disease with contemporary treatments. Since a short duration between symptom onset and diagnosis was correlated to a period of inactive disease, children suspected of having JIA should be transferred to specialised care as soon as possible.

Impact of anti‐inflammatory treatment on the onset of uveitis in juvenile idiopathic arthritis: Longitudinal analysis from a nation‐wide paediatric rheumatological database

Based on a nationwide database, this study analyzed the influence of methotrexate (MTX), tumor necrosis factor (TNF) inhibitors, and a combination of the 2 medications on uveitis occurrence in juvenile idiopathic arthritis (JIA) patients.

[Measurement of quality of life in patients with active ankylosing spondylitis being treated with infliximab-a comparison of SF-36 and SF-12].

Zusammenfassung.Hintergrund:Lebensqualität, als Teil der WHO-Gesundheitsdefinition, wird zunehmend als wichtiger Faktor zur Bewertung von Therapieerfolgen bei chronischen Erkrankungen wahrgenommen. Der international zur Zeit am häufigsten eingesetzte Fragebogen ‚Short-Form-36‘ (SF-36) zur Beurteilung der gesundheitsbezogenen Lebensqualität wurde in einer plazebokontrollierten multizentrischen Studie zur Wirksamkeit von Anti-Tumornekrosefaktor-α (Infliximab) bei 70 Patienten mit ankylosierender Spondylitis (AS) eingesetzt. Auf der Basis des sehr guten Ansprechens der Patienten auf das Medikament ergaben sich erhebliche Veränderungen der Patientenbewertung. In der vorliegenden Untersuchung wird analysiert, ob die schneller ausfüllbare kürzere Fragebogenversion SF-12 eine vergleichbare Aussagefähigkeit bezüglich der Summendimensionen für körperliche und psychische Gesundheit wie die des SF-36 bei Patienten mit ankylosierender Spondylitis hat. Dies wäre ein beträchtlicher Vorteil für zukünftige Studien z. B. für die Inzeptionskohorte für Spondyloarthritiden innerhalb des Kompetenznetzwerks. Darüber hinaus sollen die Daten der AS-Patienten mit der kürzlich veröffentlichten Normstichprobe der deutschen Normalbevölkerung verglichen werden.Methoden:Im Rahmen einer plazebokontrollierten multizentrischen Studie wurden 70 Patienten behandelt. 35 Patienten erhielten Plazebo, 35 Patienten Infliximab 5 mg/kg in Woche 0, 2 und 6. Anschließend wurden beide Gruppen mit Infliximab 5 mg/kg Körpergewicht alle 6 Wochen offen weiterbehandelt. Folgende Instrumente wurden eingesetzt: zur Messung der Krankheitsaktivität bei AS der BASDAI, für die funktionellen Beeinträchtigungen der BASFI, für die Einschränkung der Wirbelsäulenbeweglichkeit der BASMI, für Schmerzen die Numerische Rating Skala (NRS), das C-reaktive Protein (CRP) sowie für die gesundheitsbezogene Lebensqualität der SF-36. Aus den gewonnenen Daten des SF-36 wurde der SF-12 extrahiert und mit dem SF-36 hinsichtlich ihrer Übereinstimmung auf Patientenebene, ihrer gegenseitigen Korrelation, der Korrelation mit dem BASFI, Änderungssensitivität und Anzahl nicht ausgefüllter Items verglichen.Ergebnisse:Die Summendimensionen für körperliche und psychische Gesundheit für SF-12 und SF-36 waren gut vergleichbar (r=0,912 bzw. r=0,957). Alle Einzelkomponenten der gesundheitsbezogenen Lebensqualität verbesserten sich deutlich. Bei Patienten mit AS führte Infliximab zu einer deutlichen Verbesserung aller Outcome-Parameter für Krankheitsaktivität.Zusammenfassung:Die Daten zeigen, dass bei Studien mit AS-Patienten der SF-12 zur Erfassung der Lebensqualität vergleichbar gut einsetzbar ist.Summary.Background:Quality of life as a part of the WHO definition of health is an important assessment tool for measuring the success in the treatment of chronic diseases. The short form 36 questionnaire (SF-36), which is measuring health related quality of life, was used in a multicentre placebo controlled study in patients with ankylosing spondylitis (AS) treated with the anti-TNF-α antibody infliximab. As previously reported, substantial changes of almost all outcome parameters were observed in this study because of the substantial clinical improvement that is known to occur in most patients treated with anti-TNF agents. The short form 12 questionnaire (SF-12) is shorter and quicker to complete as the SF-36. The summary scales of both questionnaires were compared in this study to answer the question whether the SF-12 can also be used in AS patient populations without too much loss of information. Using the shorter from could be an advantage for further studies in patients with AS, for example, the inception cohort for spondyloarthritides within the German Network of competence in rheumatology. Furthermore the data can be compared to the German standard population.Methods:In this multicentre placebo controlled study 70 patients with active disease were enrolled: 35 AS patients received placebo, 35 were treated with infliximab, 5 mg/kg at week 0/2/6. Thereafter all patients were treated in an open study with infliximab at 5 mg/kg every 6 weeks. The disease activity (BASDAI), function (BASFI), mobility (BASMI), pain (NRS) and CRP as well as SF-36 were assessed. Data to calculate the SF-12 were extracted from the SF-36 questions and compared concerning agreement of individual levels, correlation with each other and with the BASFI, sensitivity to change and missing values.Results:All outcome parameters for disease activity as well as all subscales of health related quality of life improved in patients with active AS treated with infliximab. The comparability of the sum components for SF-12 and SF-36 were high (physical health r=0.912 and mental health r=0.957).Conclusion:These data suggest that the shorter version of the SF-36, the SF-12, is capable to measure quality of life in clinical studies with AS patients.

Outcome and Trends in Treatment of Systemic Juvenile Idiopathic Arthritis in the German National Pediatric Rheumatologic Database, 2000–2013

To investigate the clinical presentation and medical treatment of patients with systemic juvenile idiopathic arthritis (JIA) during the first year of illness. Our study focused on 3‐year outcomes in a subsample of patients who were followed up longitudinally.

[Transition clinic--it is not always a simple segue in rheumatology for adults].

ZusammenfassungIm Kindesalter beginnende chronische rheumatische Erkrankungen bleiben oft bis in das Erwachsenenalter aktiv und sind mit Einschränkungen auf körperlicher, funktioneller und sozialer Ebene verbunden. Die medizinische und psychosoziale Betreuung der Patienten muss also über das Jugendalter hinaus fortgeführt werden, was einen Wechsel von der kind-zentrierten in die erwachsenen-orientierte Gesundheitsbetreuung erforderlich macht. Jugendliche und junge Erwachsene geplant, individuell ausgerichtet und gut koordiniert in die erwachsenen-medizinische Betreuung zu überführen (=Transition), ist relevant für deren zukünftige Partizipation in der Gesellschaft und gehört heute zu einer guten klinischen Praxis. Im Rahmen der medizinischen Begleitung rheumakranker Jugendlicher beim Übergang in das Erwachsenenalter müssen neben krankheitsspezifischen Aspekten auch die entwicklungsbedingten Besonderheiten dieses Lebensabschnittes berücksichtigt werden. Die derzeitigen Betreuungsangebote für rheumakranke Jugendliche und junge Erwachsene in Deutschland sind unzureichend. Pädiatrische und internistische Rheumatologen sollten in enger Zusammenarbeit spezielle Betreuungskonzepte für diese Patientengruppe etablieren.SummaryChronic inflammatory rheumatic diseases with onset in childhood often persist into adulthood and result in a considerable number of patients in impairments of body functions and structures, activities at the individual level and participation in society. Continuation of health care beyond adolescence is, therefore, necessary. Its provision should be of high quality, coordinated, uninterrupted, patient-centred and developmentally appropriate to ensure smooth transitions between children’s and adult services and positive outcomes of transition for the young people themselves. Existing research is very persuasive on the need to improve transitions for young people with rheumatic diseases. To achieve effective transition, not only disease specific, but also aspects of growth and development have to be taken into account. Paediatric and adult rheumatologists should establish close cooperations and implement specific transition programs to meet the special health care needs of these patients.

Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis

Objectives: To assess the prevalence of overweight in patients with juvenile idiopathic arthritis (JIA) between 2003 and 2012 and to determine correlates of overweight relevant to the change in the overweight rate. Method: Annual overweight prevalence was determined in the National Paediatric Rheumatological Database (NPRD) between 2003 and 2012. The prevalence of overweight in JIA was compared to representative data from Germany in 2005. Results: The median age of JIA patients was 11.5 years and the mean disease duration 4 years. Almost 50% of JIA patients had persistent oligoarthritis, followed by rheumatoid factor (RF)-negative polyarthritis (14%). The overweight prevalence decreased significantly from 14.2% in 2003 to 8.3% in 2012 [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89–0.95]. Higher levels of physical activity and less frequent treatment with high-dose glucocorticoids (GCs) were associated with decreasing overweight rates. Systemic JIA had the highest decrease in the overweight rate over time. Patients with JIA had an overweight rate comparable to that of children and adolescents in the general population. However, systemic JIA and enthesitis-related arthritis were more likely to be associated with overweight. The use of high-dose GCs, lower functional limitations, and a lower level (or lack) of participation in school sports were significant predictors of overweight in multivariable analyses. Conclusions: The prevalence of overweight in JIA was comparable to the general population and decreased significantly over time. The decrease was associated with higher functional ability and JIA patients should be encouraged to be more physically active. The role of an elevated body mass index (BMI) in the long-term outcome of JIA needs to be addressed in future studies.