Long-term outcomes of targeted treatment in early rheumatoid arthritis

This thesis addresses various aspects regarding the treatment of patients with early, active rheumatoid arthritis. The main conclusion of this thesis is that patients with RA benefit from combination therapy on the short-term, and the treat-to-target approach determines the success of the long-term outcomes. Following this strategy, high percentages of low disease activity and remission are achieved, and even drug-free remission has shown to be realistic outcome. As a result, functional ability remains stable over time (after improvement during the first year after initiating treatment), radiographic progression is limited in most patients and excess mortality was not observed.Reumafonds, Crescendo Bioscience, Pfizer BV, Chipsoft BV, Abbvie BVUBL - phd migration 201

Biophysical and enzymatic properties of aminoglycoside adenylyltransferase AadA6 from Pseudomonas aeruginosa

AbstractThe gene coding for the aminoglycoside adenylyltransferase (aadA6) from a clinical isolate of Pseudomonas aeruginosa was cloned and expressed in Escherichia coli strain BL21(DE3)pLysS. The overexpressed enzyme (AadA6, 281 amino-acid residues) and a carboxy-terminal truncated variant molecule ([1-264]AadA6) were purified to near homogeneity and characterized. Light scattering experiments conducted under low ionic strength supported equilibrium between monomeric and homodimeric arrangements of the enzyme subunits. Circular Dichroism spectropolarimetry indicated a close structural relation to adenylate kinases. Both forms modified covalently the aminoglycosides streptomycin and spectinomycin. The enzyme required at least 5mM MgCl2 for normal Michaelis–Menten kinetics. Streptomycin exhibited a strong substrate inhibition effect at 1mM MgCl2. The truncated 17 residues at the C-terminus have little influence on protein folding, whereas they have a positive effect on the enzymic activity and stabilize dimers at high protein concentrations (>100μM). Homology modelling and docking based on known crystal structures yielded models of the central ternary complex of monomeric AadA6 with ATP and streptomycin or spectinomycin

Age affects joint space narrowing in patients with early active rheumatoid arthritis

Background: Joint space narrowing ( JSN) in rheumatoid arthritis (RA) may be a manifestation of (primary) osteoarthritis becoming more prominent with age. We investigated the severity and predictors of JSN progression among different age groups. Methods: 10-year follow-up data of the BeSt study, a randomised controlled treat-to-target trial in early RA were used. Annual X-rays of hands and feet were scored using the Sharp/van der Heijde score (SHS). Subgroups were defined by age at baseline: 55, 40<55 and <40 years. JSN progression predictors were assessed by Poisson regression. Results: Baseline JSN scores (median (IQR)) were igher in patients 55 (2.0 (0.0-6.0)) compared with the other age groups: 1.0 (0.0-3.0) 40<55 and 0.3 (0.0-3.0) <40, p<0.001. After 10 years, total JSN and SHS were similar in all age groups. In patients 55 the mean erythrocyte sedimentation rate (ESR) over time (relative risk 1.02 (95% CI 1.00 to 1.03)

Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis

Introduction: Personalized medicine is the holy grail of medicine. The EULAR recommendations for the management of rheumatoid arthritis (RA) support differential treatment between patients with baseline characteristics suggestive of a non-poor prognosis (non-PP) or poor prognosis (PP) (presence of autoantibodies, a high inflammatory activity and damage on radiographs). We aimed to determine which prognostic risk groups benefit more from initial monotherapy or initial combination therapy. Methods: 508 patients were randomized t

Drug-free holiday in patients with rheumatoid arthritis: a qualitative study to explore patients' opinion

Clinical trials have shown that in patients with long-standing low disease activity, tapering and/or stopping antirheumatic medication is a realistic option. The objective of this study is to explore patients' opinion about tapering and discontinuing antirheumatic drugs. This qualitative study is based on interviews with 20 patients with rheumatoid arthritis (RA) about RA treatment and treatment discontinuation through structured interviewing. Interviews were tape-recorded, transcribed verbatim, and screened by three assessors independently for meaning units. Not only positive emotions about drug discontinuation such as hope, happiness, and relief, but also fear and disappointment were mentioned. Some patients expect that drug discontinuation will be possible in other patients and/or themselves, while others do not expect this. The concept of increase in disease activity after discontinuing medication was mentioned, and while patients expect that disease activity will decrease again after restarting medication, they expect that this will take (too much) time. Positive emotions about the option to taper and discontinue antirheumatic medication, with negative expectations is a common combination in these RA patients. In particular, patients expect that disease activity will flare and that improvement upon restarting medication will take time. Patients' expectations and feelings should be addressed before drug tapering is attempted in a clear strategy of continued monitoring of disease activity.Pathophysiology and treatment of rheumatic disease

Drug Free Holiday In Patients With Rheumatoid Arthritis (RA): patients' Opinion

Pathophysiology and treatment of rheumatic disease

Response to 'Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis' - authors' reply

Pathophysiology and treatment of rheumatic disease

Linear extrapolation of missing radiographic change scores in clinical trials does not spuriously overestimate group radiographic changes in rheumatoid arthritis

Development and application of statistical models for medical scientific researc

Initial Combination Therapy In Early Rheumatoid Arthritis: Which Patients Benefit?

Pathophysiology and treatment of rheumatic disease