Background: Psoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at... Show moreBackground: Psoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at baseline; investigate the association of RD with swollen/tender joint counts (SJC/TJC) at baseline; and investigate the extent to which RD at baseline correlated with response to secukinumab. Methods: Pooled data (N = 1554) provided baseline radiographic bone erosion and joint space narrowing (JSN) scores at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and swollen and tender joint scores in the same joints at multiple visits. Overall patient RD and individual joints RD bone erosion and JSN scores were assessed. The association between joint activity (tenderness, swelling) and vdH-mTSS was assessed at the overall patient-level and individual joint tender, swollen scores (yes/no) and RD joint JSN and bone erosion scores at the individual joint-level. Treatment response was assessed using SJC/TJC at weeks 16 and 52 and the proportion of patients achieving minimal disease activity (MDA) over all assessments within 1 year from FUTURE 5 alone. Results: A substantial prevalence of pre-existing RD with higher prevalence of erosion than JSN was observed (86% and 60% of patients had positive erosion and JSN scores, respectively); higher RD prevalence was associated with longer time since PsA diagnosis. Joint activity was weakly associated with RD at baseline at the patient-level (Pearson's coefficients: range 0.12-0.18), but strongly associated at the individual joint-level, with a higher probability of tender/swollen joints to associate with higher JSN/erosion scores: all 42 analysed joints showed statistical significance at the 0.05 level (unadjusted) for the relationship between joint tenderness (yes/no) and its JSN score, all but one for tenderness and bone erosion scores, and all but 2 for swollen and JSN scores and for swollen and bone erosion score. Secukinumab (150/300 mg), reduced TJC and SJC across all values of baseline erosion and JSN scores at weeks 16 and 52. Patients with higher levels of RD were less likely to achieve zero tender/zero swollen joint status and had lower chance of achieving MDA. Conclusions: PsA patients showed substantial prevalence of RD at baseline that correlated with time since diagnosis, but patient's individual joint activity was strongly associated with pre-existing RD at those joints. Patients with the highest RD at baseline had a reduced likelihood of achieving zero joint count status. Show less
Ferreira, R.J.O.; Welsing, P.M.J.; Gossec, L.; Jacobs, J.W.G.; Machado, P.M.; Ndosi, M.; ... ; Silva, J.A.P. da 2018
This thesis is two-fold focused on rheumatoid arthritis and axial spondyloarthritis. It covers outstanding aspects of research methodology in the assessment of inflammation and damage in patients... Show moreThis thesis is two-fold focused on rheumatoid arthritis and axial spondyloarthritis. It covers outstanding aspects of research methodology in the assessment of inflammation and damage in patients with these diseases. The studies pertaining to the first part of the thesis focus on rheumatoid arthritis and may help to better understand the relationship between disease activity, radiographic damage and disability. More specifically, they evaluate which of the available tools (individual instruments or composite indices) is associated with radiographic damage and which of the different types of structural lesions detectable on radiographs is associated with disability. Additionally, these studies address methodological issues related to the optimal assessment of radiographic progression in clinical trials. The studies described in the second part of the thesis evaluate the benefit of supplementary tests reflecting inflammation, especially to help classifying (diagnosing) patients and to monitor disease activity. Among others, the studies described in this thesis provide data that allow a better usage of these tests in clinical practice. Overall, this thesis provide guidelines on how to assess properly rheumatoid arthritis and axial spondyloarthritis in clinical trials and in clinical practice. This precise way of assessment will lead to a better understanding and a better management of these diseases. Show less
