From inhibition of radiographic progression to maintaining structural integrity: a methodological framework for radiographic progression in rheumatoid arthritis and psoriatic arthritis clinical trials

2013 ◽  
Vol 72 (7) ◽  
pp. 1113-1117 ◽  
Author(s):  
Robert Landewé ◽  
Vibeke Strand ◽  
Désirée van der Heijde
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Structural Damage ◽  
Structural Integrity ◽  
Radiographic Progression ◽  
Methodological Framework ◽  
Drug Treatments ◽  
New Treatment ◽  
New Treatments

Usually, a clinical trial in rheumatoid arthritis and psoriatic arthritis aiming to demonstrate that a new antirheumatic drug treatment can inhibit progression of structural damage has a ‘superiority design’: The new treatment is compared to placebo or to another active treatment. Currently, many new drug treatments have shown to be able to completely suppress progression (progression rates close to zero). For largely unknown reasons, during the last 10 years, radiographic progression rates in clinical trials have gradually decreased, so that progression rates in the comparator groups are often too low to demonstrate meaningful inhibition, and thus superiority of the new treatment. We here propose an alternative framework to demonstrate that new treatments have the ability to ‘preserve structural integrity’ rather than to ‘inhibit radiographic progression’. Anno 2013, preserving structural integrity is conceptually more realistic than inhibiting radiographic progression.

scholarly journals Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001595
Author(s):  
Gerd R Burmester ◽  
Peter Nash ◽  
Bruce E Sands ◽  
Kim Papp ◽  
Lori Stockert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Special Interest ◽  
Phase 1 ◽  
Incidence Rates ◽  
Study Data ◽  
System Organ Class

ObjectivesTo analyse adverse events (AEs) of special interest across tofacitinib clinical programmes in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO), and to determine whether the incidence rates (IRs; unique patients with events per 100 patient-years) of these events are consistent across diseases.MethodsThe analysis included data from patients exposed to ≥1 dose of tofacitinib in phase 1, 2, 3 or 3b/4 clinical trials and long-term extension (LTE) studies (38 trials) in RA (23 trials), PsA (3 trials), UC (5 trials) and PsO (7 trials). All studies were completed by or before July 2019, except for one ongoing UC LTE study (data cut-off May 2019). IRs were obtained for AEs of special interest.Results13 567 patients were included in the analysis (RA: n=7964; PsA: n=783; UC: n=1157; PsO: n=3663), representing 37 066 patient-years of exposure. Maximum duration of exposure was 10.5 years (RA). AEs within the ‘infections and infestations’ System Organ Class were the most common in all diseases. Among AEs of special interest, IRs were highest for herpes zoster (non-serious and serious; 3.6, 1.8, 3.5 and 2.4 for RA, PsA, UC and PsO, respectively) and serious infections (2.5, 1.2, 1.7 and 1.3 for RA, PsA, UC and PsO, respectively). Age-adjusted and sex-adjusted mortality ratios (weighted for country) were ≤0.2 across cohorts.ConclusionsThe tofacitinib safety profile in this analysis was generally consistent across diseases and with longer term follow-up compared with previous analyses.

Biomarkers of Radiographic Progression in Psoriatic Arthritis: A Report from the GRAPPA 2011 Annual Meeting

2012 ◽  
Vol 39 (11) ◽  
pp. 2189-2192 ◽  
Author(s):  
OLIVER FITZGERALD ◽  
CHRISTOPHER T. RITCHLIN ◽  
PHILIP J. MEASE
Keyword(s):  
Psoriatic Arthritis ◽  
Annual Meeting ◽  
Structural Damage ◽  
Radiographic Progression ◽  
Clinical Markers ◽  
Sample Collection ◽  
Critical Research ◽  
Specific Protocol ◽  
Radiographic Scoring Methods ◽  
Selection Of

Clinical markers of radiographic progression have been studied in patients with psoriatic arthritis (PsA), and results have clearly confirmed the progression of radiographic damage over a 2-year period. Biomarkers of radiographic progression damage (erosion and new bone formation) have also been identified as a critical research issue in these patients. At the 2011 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members discussed development of a pivotal observational study (PsA Biodam study) to determine the validity of several soluble biomarkers in predicting structural damage in patients with PsA receiving standard therapies. Specific protocol issues discussed were the inclusion criteria, selection of candidate biomarkers, timing of sample collection, the primary radiographic outcome measure, radiographic scoring methods, possible substudies, and funding strategies.

Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucocorticoid therapy in rheumatoid arthritis clinical trials of tocilizumab or adalimumab or methotrexate monotherapy

2020 ◽  
Vol 79 (4) ◽  
pp. 460-463 ◽  
Author(s):  
Mary Safy-Khan ◽  
Johannes W G Jacobs ◽  
Maria J H de Hair ◽  
Paco M J Welsing ◽  
Michael D Edwardes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety Outcomes ◽  
Trial Outcomes

BackgroundIn rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes.ObjectivesTo determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy.MethodsData of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed.ResultsNo statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms.ConclusionNo effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.

Visualisation of structural damage as a surrogate marker of radiographic progression in patients with rheumatoid arthritis

2013 ◽  
Vol 73 (4) ◽  
pp. e24-e24 ◽  
Author(s):  
Alexander Pfeil ◽  
Peter Oelzner ◽  
Diane M Renz ◽  
Gabriele Lehmann ◽  
Gunter Wolf ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Radiographic Progression ◽  
Surrogate Marker

scholarly journals Financial accounts reports

2004 ◽  
Vol 11 (1) ◽  
Author(s):  
Colin Aaronson
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibodies ◽  
Phase I ◽  
Phase Iii ◽  
Human Monoclonal Antibodies ◽  
The Usa ◽  
Drug Treatments ◽  
The Uk ◽  
New Treatments ◽  
Antibody Technology

Cambridge Antibody Technology plc (CAT) has established itself as a leader in the development of human monoclonal antibodies as new treatments for disease, based upon its own antibody technology. By mid-June 2004 it had one drug, HUMIRATM, a treatment for rheumatoid arthritis, approved in 41 countries including the USA and the UK, drug treatments for five conditions in Phase III and a number of other drugs at Phase I or II, or at the preclinical stage.

Ultrasound in rheumatoid arthritis

2020 ◽  
pp. 195-206
Author(s):  
Andrew Filer ◽  
Maria Antonietta D’Agostino ◽  
Ilfita Sahbudin
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Early Diagnosis ◽  
Structural Damage ◽  
Structural Changes ◽  
Imaging Modality ◽  
Ultrasound Guided ◽  
Crystal Arthritis ◽  
Rheumatology Practice

Ultrasound in increasingly used in rheumatology practice in the assessment of inflammatory patient, including facilitating early diagnosis of rheumatoid arthritis (RA), predicting its outcome, measuring structural damage, and monitoring its progression. This imaging modality can visualize both inflammatory and structural changes in patients with unclassified arthritis and RA, as well as other inflammatory arthritides such as psoriatic arthritis (PsA), spondyloarthropathy (SpA), and crystal arthritis. This chapter aims to provide an overview of the recent advances of this technique for in the assessment of RA. Firstly, the principles which underpin the physics of ultrasound are summarized, followed by the musculoskeletal pathologies which are amenable to ultrasound examination. In addition, it also highlights the role of ultrasound in procedures (e.g. ultrasound-guided biopsy and ultrasound-guided injection).

scholarly journals Is Structural Damage Evaluation by Traditional Radiographs Still Relevant in Rheumatoid Arthritis Clinical Trials?

2014 ◽  
Vol 41 (11) ◽  
pp. 2325-2325
Author(s):  
BOULOS HARAOUI ◽  
JACOB KARSH ◽  
JANET E. POPE ◽  
J. CARTER THORNE ◽  
EDWARD C. KEYSTONE
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Structural Damage ◽  
Damage Evaluation

scholarly journals Current challenges in the development of new treatments for lupus

2019 ◽  
Vol 78 (6) ◽  
pp. 729-735 ◽  
Author(s):  
Maria Dall'Era ◽  
Ian N Bruce ◽  
Caroline Gordon ◽  
Susan Manzi ◽  
Janis McCaffrey ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Lupus Erythematosus ◽  
Turn Of The Millennium ◽  
Eligibility Criteria ◽  
Considerable Impact ◽  
New Treatment ◽  
New Treatments ◽  
Chronic Autoimmune Disease

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a considerable impact on patients’ quality of life. Despite the plethora of clinical trials for SLE since the turn of the millennium, only one new treatment has been approved for the condition, and the overall pace of successful drug development remains slow. Nevertheless, the myriad of clinical studies has yielded insights that have informed and refined our understanding of eligibility criteria, outcome measures and trial design in SLE. In this review, we highlight the achievements of clinical trials as well as the major pitfalls that have been identified in drug development for SLE and, in doing so, identify areas where collaboration and consensus will be important to facilitate progress.

Sign in / Sign up

Export Citation Format

Share Document