scholarly journals Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
C. A. Lechtenboehmer ◽  
T. Burkard ◽  
S. Reichenbach ◽  
U. A. Walker ◽  
A. M. Burden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Space Narrowing ◽  
Radiographic Progression ◽  
Cox Regression ◽  
Joint Space ◽  
Estimating Equation ◽  
Considerable Proportion ◽  
Hand Osteoarthritis ◽  
Increased Risk ◽  
Subchondral Sclerosis

Abstract Objectives A considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA. Methods Adult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1. Results Among 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings. Conclusions These real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.

scholarly journals POS0122 THE ASSOCIATIONS BETWEEN DISEASE MODIFYING ANTI-RHEUMATIC DRUGS AND INCIDENT, AND PROGRESSION OF, RADIOGRAPHIC HAND OSTEOARTHRITIS IN RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 272.2-273
Author(s):  
T. Burkard ◽  
C. Lechtenboehmer ◽  
S. Reichenbach ◽  
M. Hebeisen ◽  
U. Walker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Joint Space Narrowing ◽  
Radiographic Progression ◽  
Joint Space ◽  
Hand Osteoarthritis ◽  
Cohort Entry ◽  
Covariate Information ◽  
Disease Modifying ◽  
Subchondral Sclerosis

Background:Hand osteoarthritis (OA) is characterized by bone erosions, joint space remodeling, and new bone formation mainly in distal interphalangeal (DIP) joints and thereby differs from hand manifestations in rheumatoid arthritis (RA). There are conflicting data about the benefit of treatment with conventional synthetic (cs) and biologic (b) disease modifying anti-rheumatic treatment (DMARD) on DIP OA.Objectives:To assess the associations between DMARDs and incident, and progression of, radiographic DIP OA in RA patients.Methods:We performed two observational cohort studies in the longitudinal Swiss Clinical Quality Management in Rheumatic Diseases registry (SCQM) between 1997 and 2014. RA patients who had ≥2 eligible hand radiographs were included at their first eligible radiograph (baseline) and were followed until the outcome or their last eligible radiograph. Radiographs were eligible if all 8 DIP joints could be scored. Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. Incident/existing DIP OA was defined as KLS ≥2 in ≥1 DIP joint. Progression of existing DIP OA was defined as an increase of ≥1 in KLS in ≥1 DIP joint. We divided the study population into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Exposure status was defined time-dependently into mutually exclusive exposure groups: csDMARD monotherapy, bDMARD monotherapy, bDMARD/csDMARD combination therapy, past bDMARD/csDMARD therapy, or never DMARD use. Cox time-varying proportional hazard regression analyses were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) of DIP OA progression (cohort 1) or DIP OA incidence (cohort 2) associated with DMARD exposure categories (csDMARD monotherapy was the reference group because it was the largest group). Exposure and covariate information were extracted at every radiograph and other visit date. Missing covariate information was imputed using multiple imputation by chained equations. In sensitivity analyses, we repeated all analyses using generalised estimation equations (GEE).Results:Among 2234 RA patients with 5928 eligible radiographs, 1340 patients had radiographic DIP OA at cohort entry (cohort 1) and 894 were DIP OA naïve (cohort 2). In cohort 1, radiographic progression of existing DIP OA was characterized by new osteophyte formation (666, 52.4%), followed by joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), and erosion (62, 4.3%). bDMARD monotherapy was associated with an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34, 95% CI 1.07–1.69). The risk of DIP OA progression was not significant in csDMARD/bDMARD combination therapy users (adjusted HR 1.12, 95% CI 0.96–1.31), absent in past DMARD users (adjusted HR 0.96, 95% CI 0.66–1.41), and significantly lower among never DMARD users (adjusted HR 0.54, 95% CI 0.33–0.90), compared to csDMARD monotherapy users. In cohort 2, the risk of incident OA did not differ materially between treatment groups. Results from GEE analyses corroborated all findings.Conclusion:Our results from this real-world RA cohort suggest that monotherapy with bDMARDs is not associated with incident DIP OA but may increase the risk of radiographic progression of existing DIP OA when compared to csDMARDs.Acknowledgements:We thank all patients and rheumatologists involved for their contribution to the SCQM RA cohort. A list of rheumatology offices and hospitals that contribute to the SCQM registry can be found at http://www.scqm.ch/institutions. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found at http://www.scqm.ch/sponsors.Disclosure of Interests:Theresa Burkard: None declared, Christian Lechtenboehmer: None declared, Stephan Reichenbach: None declared, Monika Hebeisen: None declared, Ulrich Walker: None declared, Andrea Michelle Burden: None declared, Thomas Hügle Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: GSK, Jansen, Pfizer, Abbvie, Novartis, Roche, MSD, Sanofi, BMS, Eli Lilly, UCB

scholarly journals FRI0043 JOINT SPACE NARROWING PRECEDES EROSIVE RADIOGRAPHIC DAMAGE IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 596.2-597
Author(s):  
A. Kerschbaumer ◽  
F. Alasti ◽  
G. Supp ◽  
J. S. Smolen ◽  
D. Aletaha
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Space Narrowing ◽  
Radiographic Progression ◽  
Cox Regression ◽  
Cartilage Damage ◽  
Joint Space ◽  
Time To Progression ◽  
Research Support ◽  
Radiographic Damage ◽  
Hands And Feet

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized through symmetric polyarthritis leading to joint destruction over time in many patients. Radiographic damage is an important outcome in RA clinical trials, most commonly assessed by conventional radiographs and quantified/reported by the modified total Sharp van der Heijde Score (mTSS). The mTSS is assessing erosive (ERO) changes as well as joint space narrowing (JSN; reflecting cartilage wasting) in the small joints of the hands and feet. While erosions are the hallmarks of RA, loss of cartilage has been reported to be highly relevant for functional limitations in RA. The sequence of occurrence of these events is not completely understood.Objectives:To investigate the time to radiographic progression and assess potential differences between time-to-JSN progression and time-to-ERO progression.Methods:Radiographs of RA patients from a large prospective clinical routine cohort were scored using the mTSS by one experienced reader (G.S.) unaware of the aim of this project. Time-to-JSN and time-to-ERO was estimated using survival analyses utilizing the Kaplan-Meier estimator. In additional analyses, patients were stratified based on JSN and/or ERO damage at baseline. Further, potential predictors (demographics, csDMARD/bDMARD treatment/combination therapy) of time-to-ERO and time-to-JSN were evaluated using Cox-regression techniques. All statistical analyses were conducted using SAS v9.4 (Cary, New York, USA).Results:We assessed 798 patients longitudinally for radiographic progression. JSN occurred significantly earlier than erosions (p<0.001, Figure 1). After stratification for baseline damage (Figure 2), these differences remained significant with a shorter time-to-JSN in patients without any baseline ERO or JSN (n=44, p=0.008), patients with JSN but no ERO at baseline (n=200, p<0.001), and patients with baseline ERO and JSN (n=536, p<0.001). Only in the small group of patients with isolated erosions (without JSN) at baseline there was no difference in time-to-progression of ERO vs. JSN (n=18, p=0.241). Overall, shorter time to progression of ERO was significantly predicted by positivity for rheumatoid factor or anti-citrullinated peptide antibodies (CCP; p<0.003), as well as by erosions at baseline (p<0.001) in Cox regression. In contrast, seropositivity for neither RF nor CCP was associated with shorter time to JSN progression (p=0.226); however, baseline concomitant JSN and ERO damage did show to be a significant predictor (p<0.001).Figure 1.Time to joint space narrowing and time to erosive damage (n=798).Figure 2.Time to JSN/ERO stratified by presence or absence of ERO/JSN at baseline.Conclusion:We identified a significantly shorter time to progression of JSN compared to ERO in this longitudinal cohort of RA patients. JSN remains an important radiographic outcome, as it is strongly associated with impairment of physical function. This calls for a stronger focus on cartilage damage in RA, and a stronger consideration of JSN in routine evaluation of RA radiographs in clinical practice.Disclosure of Interests:Andreas Kerschbaumer Paid instructor for: Celgene, Speakers bureau: Andreas Kerschbaumer has received lecture fees from Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme and Pfizer., Farideh Alasti: None declared, Gabriela Supp: None declared, Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer, Roche – grant/research support, Consultant of: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – consultant, Speakers bureau: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – speaker, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB

Clustering of hand osteoarthritis progression and its relationship to progression of osteoarthritis at the knee

2013 ◽  
Vol 73 (3) ◽  
pp. 567-572 ◽  
Author(s):  
Jessica Bijsterbosch ◽  
Ingrid Meulenbelt ◽  
Iain Watt ◽  
Frits R Rosendaal ◽  
Tom W J Huizinga ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Familial Aggregation ◽  
Joint Space ◽  
Estimating Equation ◽  
Hand Osteoarthritis ◽  
Sibling Pairs ◽  
Equation Analysis ◽  
Smallest Detectable Change ◽  
Systemic Factors ◽  
Osteoarthritis Progression

ObjectiveTo investigate patterns of osteoarthritis (OA) progression within hand joints and the relationship between hand OA progression and progression of OA at the knee.MethodsRadiographic progression over 6 years, defined as change in osteophytes or joint space narrowing above the smallest detectable change, was assessed on hand and knee radiographs of 236 hand OA patients participating in the Genetics, Arthrosis and Progression (GARP) sibling pair cohort study using OARSI atlas. Clustering of radiographic progression between hand joint groups (DIP, PIP, IP-1 and CMC-1) was assessed using χ2 test. Symmetry, clustering by row and ray and familial aggregation in sibling pairs were also evaluated. The association between hand OA progression and progression of OA at the knee was assessed using generalised estimating equation analysis.ResultsThere was clustering of OA progression between hand joint groups, the strongest relationship among DIP, PIP and IP-1 joints. Other patterns were symmetry (OR 4.7 (95% CI 3.3 to 6.5)) and clustering by row (OR 2.9 (95% CI 1.9 to 4.6)) but not by ray (OR 1.3 (95% CI 0.7 to 2.4)). There was familial aggregation of hand OA progression. Patients with progression of hand OA had a higher risk for radiographic change at the knee than those without hand OA progression (OR 2.3 (95% CI 1.3 to 4.0)).ConclusionsProgression of hand OA clusters between hand joint groups, especially between IP joints, and within sibling pairs. It is associated with OA change at the knee. These findings contribute to defining hand OA subsets and suggest a role for systemic factors.

Film-Screen Vs. Digital Radiography in Rheumatoid Arthritis of the Hand

1994 ◽  
Vol 35 (4) ◽  
pp. 311-318 ◽  
Author(s):  
Á. Jónsson ◽  
A. Borg ◽  
P. Hannesson ◽  
K. Herrlin ◽  
K. Jonsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Soft Tissue ◽  
Digital Radiography ◽  
Joint Space Narrowing ◽  
Digital Images ◽  
Roc Curves ◽  
Joint Space ◽  
Hard Copy ◽  
Significant Difference ◽  
Soft Tissue Swelling

In a prospective investigation the diagnostic accuracy of film-screen and digital radiography in rheumatoid arthritis of hands was compared. Seventy hands of 36 patients with established rheumatoid arthritis were included in the study. Each of 11 joints in every hand was evaluated regarding the following radiologic parameters: soft tissue swelling, joint space narrowing, erosions and periarticular osteopenia. The digital images were obtained with storage phosphor image plates and evaluated in 2 forms; as digital hard-copy on film and on a monitor of an interactive workstation. The digital images had a resolution of either 3.33 or 5.0 lp/mm. ROC curves were constructed and comparing the area under the curves no significant difference was found between the 3 different imaging forms in either resolution group for soft tissue swelling, joint space narrowing and erosions. The film-screen image evaluation of periarticular osteopenia was significantly better than the digital hard-copy one in the 3.33 lp/mm resolution group, but no significant difference was found in the 5.0 lp/mm group. These results support the view that currently available digital systems are capable of adequate diagnostic performance.

scholarly journals High systemic bone mineral density increases the risk of incident knee OA and joint space narrowing, but not radiographic progression of existing knee OA: the MOST study

2009 ◽  
Vol 69 (01) ◽  
pp. 163-168 ◽  
Author(s):  
M C Nevitt ◽  
Y Zhang ◽  
M K Javaid ◽  
T Neogi ◽  
J R Curtis ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Joint Space Narrowing ◽  
Weight Bearing ◽  
Joint Space ◽  
Whole Body ◽  
Mineral Density ◽  
Knee Oa ◽  
Increased Risk

Objectives:Previous studies suggest that high systemic bone mineral density (BMD) is associated with incident knee osteoarthritis (OA) defined by osteophytes but not with joint space narrowing (JSN), and are inconsistent regarding BMD and progression of existing OA. The association of BMD with incident and progressive tibiofemoral OA was tested in a large prospective study of men and women aged 50–79 years with or at risk for knee OA.Methods:Baseline and 30-month weight-bearing posteroanterior and lateral knee radiographs were scored for Kellgren-Lawrence (K-L) grade, JSN and osteophytes. Incident OA was defined as the development of K-L grade ⩾2 at follow-up. All knees were classified for increases in grade of JSN and osteophytes from baseline. The association of gender-specific quartiles of baseline BMD with risk of incident and progressive OA was analysed using logistic regression, adjusting for covariates.Results:The mean (SD) age of 1754 subjects was 63.2 (7.8) years and body mass index was 29.9 (5.4) kg/m2. In knees without baseline OA, higher femoral neck and whole body BMD were associated with an increased risk of incident OA and increases in grade of JSN and osteophytes (p<0.01 for trends); adjusted odds were 2.3–2.9-fold greater in the highest compared with the lowest BMD quartiles. In knees with existing OA, progression was not significantly related to BMD.Conclusions:In knees without OA, higher systemic BMD was associated with a greater risk of the onset of JSN and K-L grade ⩾2. The role of systemic BMD in early knee OA pathogenesis warrants further investigation.

Evaluation of Serum Biomarkers Associated with Radiographic Progression in Methotrexate-naive Rheumatoid Arthritis Patients Treated with Methotrexate or Golimumab

2013 ◽  
Vol 40 (5) ◽  
pp. 590-598 ◽  
Author(s):  
Carrie Wagner ◽  
Dion Chen ◽  
Hongtao Fan ◽  
Elizabeth C. Hsia ◽  
Michael Mack ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Statistical Significance ◽  
Tumor Necrosis Factor Inhibitor ◽  
Cd40 Ligand ◽  
Joint Space ◽  
Protein Profiling ◽  
Serum Samples ◽  
Markers Of Inflammation ◽  
Factor Inhibitor

Objective.To evaluate associations between biomarkers and radiographic progression in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) treated with MTX or golimumab, a tumor necrosis factor inhibitor (with or without MTX).Methods.Serum samples from 152 MTX-naive adults with active RA who received placebo + MTX (n = 37) or golimumab (combined 50 mg + MTX or 100 mg ± MTX; n = 115) were analyzed for selected markers of inflammation and bone/cartilage turnover. One hundred patients were randomly selected for additional protein profiling using multianalyte profiles (HumanMap v1.6, Rules Based Medicine). Radiographs at baseline, Week 28, and Week 52 were scored using van der Heijde-Sharp (vdH-S) methodology. Correlations were assessed between biomarker levels (baseline and change at Week 4) and joint space narrowing, erosion, and total vdH-S scores (changes at Weeks 28 and 52). Statistical significance was defined as a correlation coefficient with an absolute value ≥ 0.3 and p < 0.05.Results.Biomarker correlations with changes in vdH-S scores at Week 28 and/or 52 were observed predominantly in the placebo + MTX group and rarely in the combined golimumab treatment group. Changes in epidermal growth factor (EGF) and CD40 ligand (CD40L) at Week 4 were positively correlated with changes in total vdH-S scores at Weeks 28 and 52 in the placebo + MTX group.Conclusion.These preliminary findings indicate that EGF and CD40L may have utility in monitoring MTX-treated patients with RA who are more likely to have radiographic progression as measured by increases in vdH-S scores.

scholarly journals Incidence of inpatient venous thromboembolism in treated patients with rheumatoid arthritis and the association with switching biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in the real-world setting

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001013 ◽  
Author(s):  
Huifang Liang ◽  
Raghava Danwada ◽  
Dianlin Guo ◽  
Jeffrey R Curtis ◽  
Ryan D Kilpatrick ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cox Regression ◽  
Incidence Rates ◽  
Disease Modifying Antirheumatic Drugs ◽  
Vein Thrombosis ◽  
Real World Setting ◽  
Increased Risk ◽  
Safety Studies ◽  
Unbiased Estimates ◽  
Deep Vein

ObjectivesTo assess incidence rates (IRs) of VTE in patients with rheumatoid arthritis (RA) on different DMARDs and DMARD switchers.MethodsAdults with RA on a DMARD between 2007 and 2017 were studied in a US claims database. Conventional synthetic DMARD (csDMARD) users, first biologic/targeted synthetic DMARD (b/tsDMARD) users and b/tsDMARD switchers (from a b/tsDMARD to another b/tsDMARD) were followed for inpatient VTE (pulmonary embolism (PE)/deep vein thrombosis (DVT)). Crude and adjusted IR and 95% CIs of VTE were estimated. HRs for VTE were estimated via Cox regression. VTE risk was also evaluated by number of switches between b/tsDMARDs and in patients without a VTE history.ResultsThe age and sex standardised IR (95% CI) of VTE (per 100 person-years) was 0.86 (0.70 to 1.03), 0.60 (0.52 to 0.68) and 0.58 (0.51 to 0.65) for b/tsDMARD switchers, first b/tsDMARD users and csDMARD users, respectively. After adjustment, b/tsDMARD switchers had an increased risk of VTE, compared with csDMARD users, HRadj (95% CI) being 1.36 (1.16 to 1.58), 1.36 (1.13 to 1.63) and 1.47 (1.18 to 1.83) for VTE, DVT and PE, respectively. Compared with first b/tsDMARD users, the HRadj (95% CI) for VTE was 1.35 (1.15 to 1.60) for first b/tsDMARD switchers and 1.48 (1.19 to 1.85) for second b/tsDMARD switchers.ConclusionsIn RA, b/tsDMARD switchers have a higher VTE risk compared with csDMARD users and first b/tsDMARD users. Switching b/tsDMARDs may be a proxy for higher disease severity or poorly controlled RA and an important confounder to consider in obtaining unbiased estimates of VTE risk in observational RA safety studies.

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