Search

Objectives: To examine the safety and effectiveness of long-term tocilizumab treatment in elderly patients with rheumatoid arthritis (RA) and patients with age-associated comorbidities., Methods: ICHIBAN (NCT01194401) was a prospective, non-interventional study that observed adult patients with active moderate-to-severe RA in German rheumatology clinics and practices for up to two years. Patients were to be treated according to the tocilizumab label. Here, we present safety and effectiveness data analysed according to patient age., Results: Of the 3,164 patients treated with at least one dose of tocilizumab, 924 patients were <50 years old, 1496 patients were 50-65 years old, and 744 patients were >65 years old at baseline. Patients >65 years had the highest baseline DAS28-ESR, CDAI, and HAQ-DI scores, along with the highest burden of comorbidities, such as diabetes, coronary heart disease, anaemia, and renal insufficiency. Under treatment with tocilizumab, patients >65 years had similar improvements in DAS28-ESR, CDAI and patient-reported outcomes (fatigue, pain, sleeplessness) with similar glucocorticoid savings compared to patient groups <65 years. Patients >65 years with late-onset RA achieved similar reductions in disease activity compared to early-onset patients. Despite numerically higher rates of adverse events (AEs), serious AEs and serious infections in patients >65 years, there were similar rates of AEs leading to withdrawal., Conclusions: Elderly patients in ICHIBAN experienced improvements similar to younger patients in most effectiveness endpoints with only slightly higher rates of AEs, indicating an overall net-positive risk-benefit ratio of tocilizumab treatment regardless of patient age.

Objectives: We aimed to measure long-term effectiveness and safety of tocilizumab in patients with rheumatoid arthritis in daily German practice., Methods: ICHIBAN was a prospective, multi-centre, non-interventional study (ML22928) that enrolled adult patients with active moderate to severe rheumatoid arthritis. Patients were to be treated according to tocilizumab label and observed for up to two years. Effectiveness outcomes included DAS28-ESR remission, EULAR response, CDAI and HAQ., Results: Overall, 3164 patients received at least one dose of tocilizumab. Patient mean age was 55.5±13.1 years (74.8% female). At baseline, 72.1% of patients had at least one comorbidity. Approximately 50.9% of patients received concomitant csDMARDs, mostly methotrexate, and 80.7% received concomitant glucocorticoids (GCs). In patients receiving GCs at baseline, the mean dose decreased from 9.32±16.36 mg/d to 4.60±4.48 mg/d at week 104. In the effectiveness population with no prior TCZ (n=2902), 61.4% of patients achieved the primary outcome, DAS28-ESR remission. Improvements were seen as early as week 4. At week 104, 77.9% of patients had DAS28-ESR low disease activity, 89.6% achieved good or moderate EULAR response, and 29.5% achieved a CDAI-based remission. Effectiveness outcomes were similar in all previous therapy subgroups. The incidence of serious infections was similar to the rates in former studies involving tocilizumab. Patients receiving GC at baseline experienced slightly higher rates of treatment-related serious adverse events, mainly infections. No new safety signals were observed., Conclusions: Long-term effectiveness and safety in ICHIBAN were in line with previously reported tocilizumab efficacy and safety studies.

Objectives: To investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease., Methods: In this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation., Results: In 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age <60 years (OR = 1.78), RAID score >2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy., Conclusions: Mild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms., Clinical Trial Registration Number: This study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483)., Competing Interests: This work was funded by Roche Pharma AG and Chugai Pharma Europe Ltd. Besides Dr. Flacke’s and Dr. Hofmann’s support at the study conception phase and the review of the statistical analysis plan by an independent statistician on behalf of Roche, Roche Pharma AG and Chugai Pharma Europe Ltd. had no further direct role in the collection, analysis, or interpretation of the data. AMS Advanced Medical Services GmbH (Mannheim, Germany) was involved in the study as a contract research organization on behalf of the study sponsors conducting the data analysis in collaboration with the scientific project leaders and supporting manuscript preparation. Drs. Englbrecht, Alten, Aringer, Baerwald, Burkhardt, Fliedner, Kleinert, Kneitz, Krueger, Schett, Schmalzing, Tausche, Tony, and Wendler received grants, honoraria, consulting fees, and/or speaking fees (less than $10,000 each) from Roche Pharma AG and Chugai Pharma Europe Ltd. Dr. Englbrecht has received speaker’s fees, compensation for consultancies or board memberships from: AbbVie, Celgene, Lilly, Mundipharma, Novartis, Pfizer, UCB. Dr. Aringer reports AbbVie, Astra Zeneca, Boehringer Ingelheim, Chugai, GSK, HEXAL, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz and Sanofi advisory boards, speaking fees and/or congress support. Dr. Baewald has received travel grants and speaking honoraria or is on advisory boards for Abbvie, Amgen, Biogen, BMS, Janssen, Lilly, MSD, Pfizer and UCB. Dr. Fliedner is on advisory boards for Abbvie, BMS, and Pfizer and has participated in meetings for UBC, Lilly, and Pfizer. Dr. Schett’s work was supported by the Metarthros program of the BMBF. Dr. Schmalzing has received speaker’s fees, travel grants, research funding, or compensation for consultancies or board memberships from: Abbvie, Actelion, BMS, Celgene, Genzyme, Hexal/Sandoz, Janssen‐Cilag, MSD, Novartis, Pfizer, Sanofi Pasteur, Shire (Baxalta), and UCB. Dr. Wendler is a member of Roche and Chugai advisory boards. Dr. Kneitz has received speaker’s fees, compensation for consultancies or board memberships of: AbbVie, Berlin Chemie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi, and UCB. Dr. Eby received fees from Roche Pharma AG for manuscript preparation and statistical analysis. Dr. Flacke is an employee of Roche Pharma AG. and Dr. Hofmann is an employee of Chugai Pharma Europe Ltd. Editorial assistance for this manuscript was provided by Physicians World Europe (Mannheim, Germany), sponsored by Roche Pharma AG. Funding by corporate entities does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To validate standard self-report questionnaires for depression screening in patients with rheumatoid arthritis (RA) and compare these measures to one another and to the Montgomery-Åsberg Depression Rating Scale (MADRS), a standardized structured interview., Methods: In 9 clinical centers across Germany, depressive symptomatology was assessed in 262 adult RA patients at baseline (T0) and at 12 ± 2 weeks followup (T1) using the World Health Organization 5-Item Well-Being Index (WHO-5), the Patient Health Questionnaire (PHQ-9), and the Beck Depression Inventory II (BDI-II). The construct validity of these depression questionnaires (using convergent and discriminant validity) was evaluated using Spearman's correlations at both time points. The test-retest reliability of the questionnaires was evaluated in RA patients who had not undergone a psychotherapeutic intervention or received antidepressants between T0 and T1. The sensitivity and the specificity of the questionnaires were calculated using the results of the MADRS, a structured interview, as the gold standard., Results: According to Spearman's correlation coefficients, all questionnaires met convergent validity criteria (ρ > |0.50|), with the BDI-II performing best, while correlations with age and disease activity for all questionnaires met the criteria for discriminant validity (ρ < |0.50|). The only questionnaire to meet the predefined retest reliability criterion (ρ ≥ 0.70) was the BDI-II (r s  = 0.77), which also achieved the best results for both sensitivity and specificity (>80%) when using the MADRS as the gold standard., Conclusion: The BDI-II best met the predefined criteria, and the PHQ-9 met most of the validity criteria, with lower sensitivity and specificity., (© 2016, American College of Rheumatology.)