Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: data from a German noninterventional observational study

Abstract

The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9–3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.

Plasma Levels of Eicosapentaenoic Acid Are Associated with Anti-TNF Responsiveness in Rheumatoid Arthritis and Inhibit the Etanercept-driven Rise in Th17 Cell Differentiationin Vitro

“…Notably, some registry studies have indeed found the use of NSAIDs to predict better response to anti-TNF, 38;39 although this association was not considered at the time to be causal, and other studies have not confirmed this. 40 Against this eicosanoid hypothesis, might be the observation that inhibition of PGE 2 production by monocytes ex vivo required a relatively high intake of EPA in a dose-response study, although this was conducted in healthy volunteers rather than patients with RA 41 Other mechanisms may also be important. In mouse models of colitis, n-3 fatty acids have recently been demonstrated to reduce Th17 cell numbers, 42;43 thought in part to reflect reduced membrane-raft responsiveness to the Th17 polarising cytokine IL-6.…”

Association of Improvement in Pain With Therapeutic Response as Determined by Individual Improvement Criteria in Patients With Rheumatoid Arthritis

“…Patients in the discovery cohort were enrolled in a 2‐year noninterventional study (NCT01077258), which has been previously described 3, and were seen between April 2004 and February 2013. Only patients with stable therapy (no changes in therapeutic agents or corticosteroid dose) between month 12 and month 24 of the study were included in discovery cohort analyses.…”

“…Because of the importance of PROs in evaluating treatment response and predicting long‐term outcomes, we utilized data from a large German noninterventional study of patients with RA receiving adalimumab during routine clinical care 3 to examine the association between PROs and the Disease Activity Score in 28 joints (DAS28), a frequently used measure of disease activity that includes 3 objective components (swollen joint count, tender joint count, and ESR) and 1 subjective component (patient global assessment of health or disease activity [PGA]). In a previous publication, we reported on the use of statistical measures to determine a critical difference (d crit ) for the minimum change associated with a significant individual patient response in disease activity as assessed by the DAS28 4.…”

A gender-medicine post hoc analysis (MetaGeM) project to test sex differences in previous observational studies in different diseases: methodology

“…8 Several clinical studies have pointed out the value of sex in predicting drug response, eg, males are more likely to respond to digoxin or to biological disease-modifying rheumatic drugs. [33][34][35] Sex-specific medicine is crucial to understand how different therapeutic needs are in men and women, and consequently to define potential different therapeutic approaches between males and females. 36 Clinical research sponsored by Novartis Farma Italy in the last decade has included several large observational studies in important medical areas, such as dermatology, 15,16,18,19 rheumatology, 17 the CNS, [22][23][24][25] and infectious diseases, 37 but none of those studies, except the aforementioned GENDER ATTENTION study, adopted a sex-specific approach in data analysis.…”