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ABSTRACT: To systematically review the literature on the efficacy and safety of paracetamol (acetaminophen) in the management of pain in inflammatory arthritis.
A systematic search was performed in Medline, Embase, the Cochrane Library, and 2008/2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) conference abstracts for clinical trials and observational studies of paracetamol in patients with inflammatory arthritis. Included trials were appraised for risk of bias, and relevant study details were abstracted. Efficacy was assessed from clinical trials using improvement in pain as the outcome measure, and safety was assessed using total adverse events and withdrawals due to adverse events as outcome measures. Safety data from observational studies were assessed separately.
Eleven articles containing 12 clinical trials and 1 observational study were identified, all in patients with rheumatoid arthritis. The trials were of short duration, used atypical doses of paracetamol, and all had a high risk of bias. Overall, there was weak evidence of a benefit of paracetamol over placebo and an additive benefit of paracetamol in combination with nonsteroidal antiinflammatory drugs (NSAID). The benefit of paracetamol to NSAID alone was uncertain. No significant differences in safety were seen in the limited clinical trial data. One cohort study showed an increased rate of serious gastrointestinal events with paracetamol over NSAID when used concurrently with corticosteroids and other analgesics, but had significant methodological limitations.
There is weak evidence for the efficacy of paracetamol in patients with inflammatory arthritis, and insufficient disease-specific safety data to draw conclusions.
Journal of Rheumatology Supplement 09/2012; 90:11-6.
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ABSTRACT: Pain in inflammatory arthritis (IA) is common and often multifactorial, and many different pharmacotherapeutic agents are routinely used for pain management. There are concerns that some current pain pharmacotherapies may increase the risk of adverse events in patients with concurrent cardiovascular (CV) or renal disease.
A systematic literature review was performed searching Medline, Embase, Cochrane Central Register of Controlled Trials, DARE, and Cochrane Database of Systematic Reviews. We also hand-searched conference proceedings for the American College of Rheumatology and the European League Against Rheumatism for 2008-2009.
Our search identified 4782 studies, of which 190 were included for detailed review, but none met the inclusion criteria for our review. We identified 1 study of etoricoxib and diclofenac in non-IA populations [osteoarthritis (OA) or mixed OA and rheumatoid arthritis]. In that study, the presence of CV disease increased the likelihood of a further CV event 3-fold. Patients with 2 or more CV risk factors showed a 2-fold increased likelihood of adverse CV events.
Our review has highlighted a lack of specific evidence to guide clinicians in the management of pain in patients with IA and coexistent CV or renal disease. In the absence of this evidence, we suggest clinicians use nonsteroidal antiinflammatory drugs (NSAID) with caution in patients with preexisting CV disease or ≥ 2 CV risk factors. There is currently no evidence to advise clinicians considering other pain pharmacotherapies in the context of CV comorbidities. Current guidelines regarding the use of NSAID and opioids in moderate to severe renal impairment should also be applied to the IA population.
Journal of Rheumatology Supplement 09/2012; 90:81-4.
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ABSTRACT: To systematically review the safety of various pain therapies used during pregnancy and lactation in patients with inflammatory arthritis.
A systematic literature review was performed in Medline, Embase, the Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism 2008-2009 meeting abstracts, as part of the multinational 3e (Evidence, Expertise, Exchange) Initiative for generating practical recommendations about Pain Management by Pharmacotherapy in Inflammatory Arthritis. Articles fulfilling predefined inclusion criteria were reviewed, and quality appraisal was performed.
The search yielded a total of 3974 articles and 7 abstracts. The only study that fulfilled the criteria for pain therapies in pregnancy was a systematic review published in 2008, evaluating the effects of nonsteroidal antiinflammatory drug (NSAID) use during pregnancy in patients with rheumatic conditions. Two of the 3 studies reviewed in the 2008 publication could be included in our current review. No studies were included in the review in relation to lactation. A total of 204 malformations were identified among infants exposed to NSAID, with an OR of 1.04. The number of identified cardiac defects was higher than expected, with an OR of 1.86. There seemed to be no specificity for the type of NSAID used. Among the 6 infants with orofacial clefts, 5 occurred with naproxen use and 1 with ibuprofen.
Only 2 studies evaluating the risk of NSAID use in patients with inflammatory arthritis were identified, with results suggesting a higher rate of cardiac malformations in infants exposed to NSAID during the first trimester. No studies evaluating the effects of other treatments, such as paracetamol, corticosteroids, muscle relaxants, neuromodulators, antidepressants, opioids, or opioid-like therapy in the specific context of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or spondyloarthritis, and no studies with respect to lactation were identified. Research is needed to improve the risk-benefit ratio of the use of pain therapies for inflammatory arthritis during pregnancy.
Journal of Rheumatology Supplement 09/2012; 90:59-61.
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ABSTRACT: To systematically review the literature on the safety of using nonsteroidal antiinflammatory drugs (NSAID) and/or paracetamol in people receiving methotrexate (MTX) for inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations.
A systematic literature review was performed using the Cochrane Library, Medline, Embase, and conference proceedings for the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) for 2008-2009. The search aimed to identify studies describing adverse events (AE) with the concurrent use of paracetamol and/or NSAID in people taking MTX for IA. Articles fulfilling our predefined inclusion criteria were systematically reviewed and quality appraised.
Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis (RA) using various NSAID; there were no identified studies for other forms of IA or with paracetamol. Of the studies examining concurrent use of MTX and NSAID, there were no reported adverse effects on lung, liver, or renal function, and no increase in MTX withdrawal or in major toxic reactions. However, transient thrombocytopenia was demonstrated in 1 study. Looking at specific NSAID, there were no clinically significant AE with concomitant piroxicam or etodolac, and only mild AE with celecoxib or etoricoxib. Antiinflammatory dose aspirin was demonstrated to have an adverse effect on liver and renal function.
In the management of RA, concurrent use of NSAID with MTX appears to be safe, provided appropriate monitoring is performed. The use of antiinflammatory doses of aspirin should be avoided.
Journal of Rheumatology Supplement 09/2012; 90:62-73.
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ABSTRACT: Presence and levels of antibodies contribute to the classification of rheumatoid arthritis. We investigated the longitudinal course of anti-citrullinated protein antibodies (ACPA) and immunoglobin M (IgM) rheumatoid factor (RF) during the first year after arthritis onset in patients with very short disease duration.
Patients (aged 18-75 years) with ≥ 1 swollen joint of ≤ 16 weeks' duration had assessments of ACPA (2nd generation anti-cyclic citrullinated peptide antibodies, anti-CCP2) and IgM RF at inclusion and after 3, 6, and 12 months. Frequencies of seroconversions (negative to positive and vice versa) and changes in antibody levels during followup were determined.
A total of 281 early arthritis patients (median duration of joint swelling 32 days, 14.2% ACPA positives, 12.8% IgM RF positives) with 978 longitudinally collected serum samples were included. Only 5 patients (1.8%) negative for both antibodies at baseline turned antibody-positive during followup, while 9 antibody-positive patients (3.2%) turned antibody-negative. ACPA was more stable than RF regarding both status and levels.
Antibody status (ACPA/RF) is a stable phenotype in very early arthritis, as seroconversion was only found in 5% of patients. Repeated measurement of ACPA or RF during the first year after onset of arthritis does not offer major additional information.
The Journal of Rheumatology 10/2011; 38(11):2336-41. · 3.69 Impact Factor
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ABSTRACT: Studies of Caucasian populations have shown conflicting results concerning the association between a promoter polymorphism -169T>C of the Fc receptor-like 3 (FCRL3) gene and rheumatoid arthritis (RA). It is unknown whether FCRL3 is associated with autoantibody status and disease severity. We investigated associations between FCRL3 -169T>C and autoantibody status and joint damage in patients with RA.
A total of 652 Norwegian patients with RA from 2 cohorts and 981 Norwegian controls, previously genotyped for FCRL3 -169T>C (rs7528684), were studied. Data on anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were available. The EURIDISS cohort (disease duration ≤ 4 yrs at baseline) was followed longitudinally, with assessment of radiographic hand damage at baseline and after 10 years (n = 117) according to the van der Heijde-modified Sharp score.
We found significant associations with ACPA-positive RA for both the C allele (OR 1.28, 95% CI 1.08-1.52, p = 0.004) and the C/C genotype (OR 1.57, 95% CI 1.18-2.10, p = 0.002). Similar associations were seen with RF-positive RA. No association was found with ACPA-negative or RF-negative RA. The C/C genotype was found to be associated with 10-year radiographic progression in multivariate linear and logistic regression analyses, after adjustment for ACPA, erythrocyte sedimentation rate, age, and sex.
The promoter polymorphism of FCRL3 was associated with autoantibody-positive RA. Despite the low number of patients, the C/C genotype of the FCRL3 polymorphism consistently and independently predicted radiographic progression. These findings suggest that FCRL3 is involved in both disease susceptibility and progression.
The Journal of Rheumatology 09/2011; 38(11):2329-35. · 3.69 Impact Factor
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ABSTRACT: The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess disease activity in ankylosing spondylitis (AS). Criteria for disease activity states and improvement scores are important for use in clinical practice, observational studies, and clinical trials, and have been proposed by the Assessment of SpondyloArthritis international Society (ASAS). At OMERACT 10, our aim was to obtain endorsement from OMERACT for the ASDAS disease activity states and response criteria proposed by the ASAS membership. This article summarizes the associated discussions, the scientific basis of the validation process, and the results from the voting sessions, and identifies areas for research using the ASDAS. OMERACT participants agreed with the selection of cutoff values, which now have the combined endorsement of ASAS and OMERACT and are ready to be used in clinical practice and in research settings.
The Journal of Rheumatology 07/2011; 38(7):1502-6. · 3.69 Impact Factor
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ABSTRACT: Arthropathies are a major clinical problem in patients with inflammatory bowel disease (IBD). Often it is difficult to control the articular symptoms with the anti-inflammatory strategies used for IBD. Studies evaluating specific treatments aimed at articular manifestations in patients with IBD are rare. Although there has been considerable interest in the gut-joint axis over the last decade, the pathophysiological mechanisms driving IBD-associated arthropathy are still unknown. Recently, interest in the multidisciplinary approach to patients with IBD and arthropathy has been increasing. New research and clinical projects aimed at understanding the mechanisms of disease may advance the development of effective therapies. In this review, the pathophysiology of IBD-associated arthropathy is discussed, as well as clinical manifestations, the classification and current therapeutic strategies.
Gut 05/2011; 60(10):1426-35. · 10.11 Impact Factor
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Journal of Rheumatology Supplement 03/2011; 87:1-2.
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ABSTRACT: To perform a systematic literature review on the diagnostic and predictive value of conventional radiographs (CR) in patients with undifferentiated arthritis (UA).
We performed an extended search using Medline, Embase, the Cochrane Library, and abstracts from the 2007 and 2008 meetings of the American College of Rheumatology and the European League Against Rheumatism. Articles were included based on predefined inclusion criteria, and quality was assessed by using validated quality scales.
In total, 25 articles were included from 6003 retrieved references. Five articles described a pure UA population, 20 articles described a mixed population [mostly rheumatoid arthritis (RA) and UA]. In studies on UA, erosions on CR were strong predictors of RA diagnosis [positive likelihood ratio (LR+) 3.5-10.9; odds ratio 7.6 and 8.7). In a more heterogeneous mixed population, 20 studies reporting on 11 cohorts found a relationship between CR findings and subsequent diagnosis of RA. LR+ for erosions and/or bony decalcifications ranged from 1.8 to 9.7, and there was greater prevalence of erosions and higher Sharp-van der Heijde score in the RA group at followup. With regard to prognosis in both UA and mixed populations, an association was found between number of abnormalities on CR and poor outcome.
Several studies, in pure UA and mixed populations, clearly demonstrate that CR are helpful in predicting future diagnosis of RA or worse prognosis. However, absence of abnormalities on CR does not sufficiently exclude RA or other unfavorable outcome.
Journal of Rheumatology Supplement 03/2011; 87:26-30.
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Glen Hazlewood,
Daniel Aletaha,
Loreto Carmona,
Robert B M Landewé, Désirée M van der Heijde,
Johannes W J Bijlsma,
Vivian P Bykerk,
Helena Canhão,
Anca I Catrina,
Patrick Durez, [......],
Pindaro Martinez-Osuna,
Carlomaurizio Montecucco,
Mikkel Ostergaard,
Natali Serra-Bonett,
Ricardo M Xavier,
Jane Zochling,
Pedro Machado,
Kristof Thevissen,
Ward Vercoutere,
Claire Bombardier
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ABSTRACT: To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA).
An algorithm for identification of UPIA was developed by consensus during a roundtable meeting with an expert panel. It was informed by systematic reviews of the literature used to generate 10 recommendations for the investigation and followup of UPIA through the 3e initiative. The final recommendations from the 3e UPIA Initiative were made available to the panel to guide development of the algorithm. The algorithm drew on the clinical experience of the consensus panel and evidence from the literature where available.
In patients presenting with joint swelling a thorough evaluation is required prior to diagnosing UPIA. After excluding trauma, the differential diagnosis should be formulated based on history and physical examination. A minimum set of investigations is suggested for all patients, with additional ones dependent on the most probable differential diagnoses. The diagnosis of UPIA can be made if, following these evaluations, a more specific diagnosis is not reached. Once a diagnosis of UPIA is established, patients should be closely followed as they may progress to a specific diagnosis, remit, or persist as UPIA, and additional investigations may be required over time.
Our algorithm presents a diagnostic approach to identifying UPIA in patients presenting with joint swelling, incorporating the dynamic nature of the condition with the potential to evolve over time.
Journal of Rheumatology Supplement 03/2011; 87:54-8.
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ABSTRACT: To perform a systematic literature review of the diagnostic and prognostic value of magnetic resonance imaging (MRI) and ultrasound (US) in patients with undifferentiated peripheral inflammatory arthritis (UPIA), and to assess if MRI and US should be done at baseline and repeated, and if so, at what interval.
Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism meetings were searched for diagnostic and prognostic studies of any duration examining the ability of MRI/US to predict outcome of patients with UPIA. Sensitivity, specificity, predictive values, and positive/negative likelihood ratios (LR+/LR-) were calculated. When available, odds ratios were extracted. Quality was appraised using validated scales.
Regarding MRI, 11 out of 2595 screened references were included: 2 described pure undifferentiated arthritis (UA) populations and 9, mixed populations. Bone edema (LR+ 4.5) and combination of a distinct MRI synovitis and erosion pattern (LR+ 4.8) increased probability of developing rheumatoid arthritis (RA). Absence of MRI synovitis (LR- 0.2) and absence of a distinct synovitis pattern (LR- 0) decreased probability of developing RA. Regarding US, 2 out of 2111 references were included, both mixed populations; no data could be extrapolated for UPIA.
MRI bone edema and combined synovitis and erosion pattern seem useful in predicting development of RA from UPIA. The value of US in UPIA remains to be determined. The absence of MRI synovitis seems useful in excluding development of RA. No data were found about the value of repeating MRI/US. Studies evaluating MRI/US in UPIA are scarce, but current knowledge strongly encourages further testing in UA.
Journal of Rheumatology Supplement 03/2011; 87:31-7.
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ABSTRACT: Inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are associated with a variety of extraintestinal manifestations. The most common extraintestinal manifestation, articular involvement, occurs in 16% to 33% of inflammatory bowel disease patients. These arthropathies may increase morbidity, resulting in a worse quality of life compared with inflammatory bowel disease patients without arthropathies. Thus, arthropathies in inflammatory bowel diseases represent a major medical problem in these patients. Arthritis associated with inflammatory bowel diseases is one of the diseases captured under the umbrella of spondyloarthritis. Spondyloarthritis is a group of inflammatory diseases with overlapping features and is linked to Human Leukocyte Antigen-B27. Arthropathy in inflammatory bowel diseases is clinically divided into peripheral and axial involvement. Peripheral arthritis often flares with relapses of bowel disease resulting in a different treatment approach than axial arthritis in which the course is independent of inflammatory bowel disease activity. Definitions, prevalence, pathophysiology and treatment of the arthropathies commonly seen in inflammatory bowel diseases such as peripheral arthritis, dactylitis, enthesitis, arthralgia, sacroiliitis, inflammatory back pain and ankylosing spondylitis are summarized.
Journal of Crohn s and Colitis 09/2010; 4(3):257-68. · 2.57 Impact Factor
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Jie Zhang,
David T Redden,
Gerald McGwin,
Leigh F Callahan,
Edwin A Smith,
Graciela S Alarcón,
Larry W Moreland, Désirée M van der Heijde,
Elizabeth E Brown,
Donna K Arnett,
Ted R Mikuls,
S Louis Bridges
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ABSTRACT: To examine the association between baseline bone mineral density (BMD) and radiographic damage at 3 years of disease duration in a longitudinal cohort of African Americans with recent-onset rheumatoid arthritis (RA).
African American RA patients with a disease duration of <2 years (n = 141) were included in the study. All patients underwent baseline BMD measurements (femoral neck and/or lumbar spine) using dual x-ray absorptiometry. T scores were calculated using normative data from the general population of African Americans. Patients were categorized as having osteopenia/osteoporosis (T score less than or equal to -1) or as being healthy. Hand and wrist radiographs, obtained at baseline and at 3 years of disease duration, were scored using the modified Sharp/van der Heijde method. The association between baseline BMD and total radiographic score at 3 years of disease was examined using multivariable negative binomial regression.
At baseline, the mean age and the mean disease duration were 52.4 years and 14.8 months, respectively; 85.1% of the patients were women. The average total radiographic scores at baseline and at 3 years of disease were 2.4 and 5.7, respectively. In the final reduced multivariable model, adjusting for age, sex, anti-cyclic citrullinated peptide antibody positivity, and the presence of radiographic damage at baseline, the total radiographic score at 3 years disease in patients with osteopenia/osteoporosis of the femoral neck was twice that in patients with normal bone density, and the difference was statistically significant (P = 0.0084). No association between lumbar spine osteopenia/osteoporosis and radiographic score was found.
Our findings suggest that reduced generalized BMD may be a predictor of future radiographic damage and support the hypothesis that radiographic damage and reduced generalized BMD in RA patients may share a common pathogenic mechanism.
Arthritis & Rheumatism 08/2010; 62(8):2219-26. · 7.87 Impact Factor
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Paula I Burgos,
Zenoria L Causey,
Ashutosh Tamhane,
James M Kelley,
Elizabeth E Brown,
Laura B Hughes,
Maria I Danila,
Amalia van Everdingen,
Doyt L Conn,
Beth L Jonas,
Leigh F Callahan,
Edwin A Smith,
Richard D Brasington,
Larry W Moreland, Désirée M van der Heijde,
Graciela S Alarcón,
S Louis Bridges
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ABSTRACT: To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans.
Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors.
Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score>0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj=8.08 (95% confidence interval (CI): 1.60-40.89), P=0.01 and ORadj=2.97 (95% CI, 1.08 to 8.17), P=0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj=8.45 (95% CI, 1.57 to 45.44), P=0.01, and ORadj=3.57 (95% CI, 1.18 to 10.76), P=0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj=4.52 (95% CI, 1.20 to 17.03), P=0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls.
We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations.
Arthritis research & therapy 05/2010; 12(3):R75. · 4.27 Impact Factor
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S Louis Bridges,
Zenoria L Causey,
Paula I Burgos,
B Quynh N Huynh,
Laura B Hughes,
Maria I Danila,
Amalia van Everdingen,
Stephanie Ledbetter,
Doyt L Conn,
Ashutosh Tamhane,
Andrew O Westfall,
Beth L Jonas,
Leigh F Callahan,
Edwin A Smith,
Richard Brasington,
Larry W Moreland,
Graciela S Alarcón, Désirée M van der Heijde
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ABSTRACT: To describe radiographic changes in African Americans with rheumatoid arthritis (RA) from the Consortium for the Longitudinal Evaluations of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry, a multicenter observational study.
Self-declared African American patients were enrolled in CLEAR I, a longitudinal cohort of early RA (disease duration of <2 years) from 2000 to 2005, or in CLEAR II, a cross-sectional cohort (any disease duration) from 2006 to the present. Demographic and clinical data were obtained, and sets of hand/wrist and foot radiographs were scored using the modified Sharp/van der Heijde scoring system.
A total of 357 and 418 patients were enrolled in CLEAR I and CLEAR II, respectively. We report here an interim analysis of radiographic severity in these patients. For the CLEAR I cohort, 294 patients had a mean radiographic score of 2.89 at the baseline visit; 32.0% showed either erosions (25.9%) or joint space narrowing (JSN; 19.4%). At the 36-month visit, the mean score was 5.65; 44.2% had erosions, 41.5% had JSN, and 54.4% had either. Among those patients without radiographic damage at baseline, 18.9% had progressed at the 36-month visit, compared with 57.1% of those with baseline damage (P < 0.0001). For the CLEAR II cohort, of 167 patients with RA of any duration, 65.3% exhibited joint erosions, 65.3% exhibited JSN, and 74.8% exhibited either. The mean radiographic score was 33.42.
To our knowledge, this is the largest radiographic study of African American RA patients. Damage occurs early in the disease and is associated with radiographic progression at 3 years of disease duration. The CLEAR Registry will provide a valuable resource for future analyses of genetic, clinical, and environmental factors associated with radiographic severity of RA in African Americans.
Arthritis care & research. 05/2010; 62(5):624-31.
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Michael P M van der Linden,
Anouk L Feitsma,
Saskia le Cessie,
Marlena Kern,
Lina M Olsson,
Soumya Raychaudhuri,
Ann B Begovich,
Monica Chang,
Joseph J Catanese,
Fina A S Kurreeman,
Jessica van Nies, Désirée M van der Heijde,
Peter K Gregersen,
Tom W J Huizinga,
René E M Toes,
Annette H M van der Helm-Van Mil
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ABSTRACT: The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction.
RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n=563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti-citrullinated protein antibody (ACPA)-positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study.
The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P=0.003 and P=0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P=0.021).
A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA-positive RA. Our findings provide one of the first non-HLA-related genetic severity factors that has been replicated.
Arthritis & Rheumatism 08/2009; 60(8):2242-7. · 7.87 Impact Factor
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ABSTRACT: Joint destruction in rheumatoid arthritis (RA) was until recently seen as an irreversible state. Lately, it was found that repair of bone erosions occurs; however, little is known about its prevalence.
To investigate the frequency of repair and patients' characteristics associated with repair in an inception cohort.
250 patients with RA, included in the Leiden Early Arthritis Clinic between 1993 and 2000 and treated with conventional disease-modifying antirheumatic drugs, were studied (mean follow-up 10.1 years). Radiographs obtained annually were scored using the Sharp-van der Heijde method, initially aware of the chronology. Patients with a negative change in erosion scores on subsequent radiographs were selected and their series of radiographs were re-scored with concealed time sequence by three readers. Repair was defined as agreement between two readers of a negative change in erosion scores that persisted for at least 2 years.
Repair was identified in 32 joints in 18 patients (7.2%). Patients with repair had a greater prevalence of autoantibodies (rheumatoid arthritis, anti-citrullinated protein antibody) and a higher level of joint destruction. In the joints with repair, arthritis was absent in the 2 years preceding repair.
Repair occurred in 7.2% of the patients with RA, particularly in clinically inactive joints in patients with severe destructive disease.
Annals of the rheumatic diseases 06/2009; 69(4):727-9. · 8.11 Impact Factor
