Search

Objective: To define meaningful within-patient change (MWPC) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)., Methods: Data were analyzed separately from 3 phase III clinical trials (ClinicalTrials.gov: NCT02697773, NCT02709486, NCT02528188) of tanezumab, a novel treatment intended for the relief of signs and symptoms of moderate-to-severe osteoarthritis (OA), administered subcutaneously every 8 weeks. Patients with moderate-to-severe OA of the hip or knee completed the WOMAC and patient global assessment of OA (PGA-OA) at regular timepoints. A repeated measures longitudinal model with change in WOMAC Pain, Physical Function, or Stiffness domain score as the outcome and change in PGA-OA as the anchor was used to establish MWPC for WOMAC domains., Results: In the 3 studies, there were 688, 844, and 2948 subjects available for analyses, respectively. Analysis showed that a linear relationship between changes in WOMAC domains and changes in PGA-OA was supported and justified. Moreover, the relationships between these changes were very similar for 2 trials and close for the third. The estimated MWPC for the 3 WOMAC domains were from 0.84-1.16 (0-10 numerical rating scale) and from 12.50-16.23%, depending on study and domain, that corresponded to a 1-category change on PGA-OA. For a 2-category change those values were from 1.68-2.31 and from 25.01-32.46%, respectively., Conclusion: These results establish MWPCs for WOMAC domains, at the individual patient level, for patients with moderate-to-severe OA of the hip or knee. [ClinicalTrials.gov: NCT02697773, NCT02709486, and NCT02528188]., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: To investigate the metabolic syndrome (MetS) association with radiographic and symptomatic hand osteoarthritis (HOA)., Methods: Using 1:2 propensity score matching for relevant confounders, we included 2509 participants (896 MetS positive and 1613 MetS negative) from the Osteoarthritis Initiative dataset. MetS and its components, according to the International Diabetes Federation criteria, were extracted from baseline data, and included hypertension, abdominal obesity, dyslipidemia, and diabetes. We scored distinct hand joints based on the modified Kellgren-Lawrence (mKL) grade of baseline radiographs, with HOA defined as mKL ≥ 2. In the cross-sectional analysis, we investigated the association between MetS and its components with radiographic HOA and the presence of nodal and erosive HOA phenotypes using regression models. In the longitudinal analysis, we performed Cox regression analysis for hand pain incidence in follow-up visits., Results: MetS was associated with higher odds of radiographic HOA, including the number of joints with OA (OR 1.32, 95% CI 1.08-1.62), the sum of joints mKLs (OR 2.42, 95% CI 1.24-4.71), mainly in distal interphalangeal joints (DIPs) and proximal interphalangeal joints (PIPs; OR 1.52, 95% CI 1.08-2.14 and OR 1.38, 95% CI 1.09-1.75, respectively), but not metacarpophalangeal (MCP) and first carpometacarpal (CMC1) joints. Hand pain incidence during follow-up was higher with MetS presence (HR 1.25, 95% CI 1.07-1.47). The erosive HOA phenotype and joints' nodal involvement were more frequent with MetS (OR 1.40, 95% CI 1.01-1.97 and OR 1.28, 95% CI 1.02-1.60, respectively)., Conclusion: MetS, a potentially modifiable risk factor, is associated with radiographic DIP and PIP OA and longitudinal hand pain incidence while sparing MCPs and CMC1s. Nodal and erosive HOA phenotypes are associated with MetS, suggestive of possible distinct pathophysiology., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: To evaluate the association of baseline serum level of vitamin D with disease activity, disability, and radiographic damage over the first year in early rheumatoid arthritis (RA)., Methods: Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. Levels of 25-hydroxy vitamin D2 and D3 were measured at baseline. Baseline associations between vitamin D level and 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and van der Heijde modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitamin D level and radiographic progression (mTSS increased by ≥ 1 point) or disability (HAQ-DI ≥ 0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes., Results: Among 813 patients with early arthritis, data for 645 patients with RA were analyzed. Vitamin D level was < 10 ng/mL (deficiency, group 1), 10-29.9 ng/mL (low level, group 2), and ≥ 30 ng/mL (normal, group 3) for 114 (17.7%), 415 (64.54%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitamin D deficiency compared with groups 2 and 3 combined ( P = 0.007 and P = 0.001, respectively), as was mean mTSS, but not significantly (p = 0.076). On multivariate analysis, baseline vitamin D deficiency was associated with HAQ-DI at 6 months (OR 1.70) and mTSS at 12 months (OR 1.76)., Conclusion: Vitamin D deficiency was associated with more active and severe disease at baseline and may predict disability and radiographic progression over 1 year in early RA patients. [ClinicalTrials.gov: NCT03666091].

Objective: To evaluate hand osteoarthritis tools for core instrument set development., Methods: For OMERACT 2018, a systematic literature review and advances in instrument validation were presented., Results: Visual analog and numerical rating scales were considered valuable for pain and patient's global assessment, despite heterogeneous phrasing and missing psychometric evidence for some aspects. The Modified Intermittent and Constant Osteoarthritis Pain scale was lacking evidence. The Michigan Hand Outcomes Questionnaire had advantages above other pain/function questionnaires. The Hand Mobility in Scleroderma scale was valid, although responsiveness was questioned. Potential joint activity instruments were evaluated., Conclusion: The development of the core instrument set is progressing, and a research agenda was also developed.

Objective: To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1β (IL-1β) and related to cartilage catabolism in murine osteoblasts., Methods: Osteoblasts were obtained from Swiss mice and cultured for 3 weeks. HA-treated osteoblasts were incubated with 100 μg/ml HA during the last week of culture, then stimulated with IL-1β (10 ng/ml) for 24 h. The expression of matrix metalloproteinases 3 and 13 (MMP-3 and MMP-13), ADAMTS-4 and ADAMTS-5, tissue inhibitor of metalloproteinases (TIMP), osteoprotegerin, and receptor activator of nuclear factor-κB ligand (RANKL) was determined by real-time polymerase chain reaction. MMP-3 and MMP-13 release was assessed by Western blot analysis., Results: IL-1β increased the mRNA levels of MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5 and release of MMP-3 and MMP-13. Seven days of HA treatment significantly prevented the IL-1β-increased mRNA levels of MMP-3 (-61%, p < 0.01), MMP-13 (-56%, p < 0.01), ADAMTS-4 (-58%, p < 0.05), ADAMTS-5 (-52%, p < 0.01), and RANKL (-49%, p < 0.05), but not TIMP. As well, IL-1β-induced production of MMP-3 and MMP-13 was inhibited, by 27% (p < 0.01) and 40% (p < 0.01), respectively., Conclusion: In an inflammatory context in murine osteoblasts, HA can inhibit the expression of MMP and ADAMTS. Because HA can counteract the production of these mediators in chondrocytes, its beneficial effect in osteoarthritis may be due to its action on cartilage and subchondral bone.

Objective: To report the 5-year outcome of a large prospective cohort of patients with very early rheumatoid arthritis (RA), and to identify factors predictive of outcome., Methods: Patients were recruited if they had early arthritis of < 6 months' duration, had a high probability of developing RA, and had never been prescribed disease-modifying antirheumatic drugs (DMARD) or steroids. Logistic regression analysis was used to determine factors that predict outcome., Results: We included 813 patients from December 2002 to April 2005. Age was 48.1 ± 12.6 years, delay before referral 103.1 ± 52.4 days, 28-joint Disease Activity Score (DAS28) 5.1 ± 1.3, Health Assessment Questionnaire (HAQ) 1.0 ± 0.7; 45.8% and 38.7% had rheumatoid factor or antibodies to cyclic citrullinated peptide (anti-CCP), respectively; 22% had hand or foot erosions; 78.5% fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8% during followup. At 5 years, 573 patients were evaluated. The outcome was mild for most patients: disease activity (median DAS28 = 2.5) and HAQ disability (median 0.3) were well controlled over time; 50.6% achieved DAS28 remission and 64.7% low disease activity. Radiographic progression was low (2.9 Sharp unit/year) and only a few patients required joint surgery. Nevertheless, some patients developed new comorbidities. During the 5 years, 82.7% of patients had received at least 1 DMARD (methotrexate, 65.9%), 18.3% a biological DMARD, and about 60% prednisone at least once. Anti-CCP was the best predictor of remaining in the cohort for 5 years, of prescription of synthetic or biologic DMARD, and of radiographic progression., Conclusion: The 5-year outcome of an early RA cohort in the 2000s was described. Anti-CCP was a robust predictor of outcome. The generally good 5-year outcome could be related to early referral and early effective treatment, key processes in the management of early RA in daily practice.

Objective: To evaluate the efficacy and safety of rituximab (RTX) in several subsets of spondyloarthritis (SpA) using the data of the AIR (Autoimmunity and Rituximab) registry., Methods: All patients receiving RTX for SpA, and prospectively included in the AIR registry from September 2005 to September 2010, were retrospectively analyzed. The response to treatment was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index for axial disease, joint count for peripheral disease, and C-reactive protein reduction., Results: Among the 595 patients included in the AIR registry, 26 patients with SpA from 13 centers were reported: ankylosing spondylitis (10), undifferentiated SpA (7), and psoriatic arthritis (9). Mean disease duration was 8.8 years (range 1-40). The extraarticular features found were psoriasis, 12 cases; uveitis, 4 cases; and Crohn's disease, 3 cases. The mean number of disease-modifying antirheumatic drugs before RTX was 2.4; previous anti-tumor necrosis factor (TNF) agents were taken in 23 cases. The mean number of RTX courses was 1.5 (range 1-5), with a total of 35.6 patient-years. Efficacy was noted in 11/23 cases: 3 out of 3 anti-TNF-naive patients and 8 out of 20 anti-TNF nonresponder patients. No predictive factors of response could be identified, particularly in diagnosis subsets or clinical presentation (axial or peripheral)., Conclusion: In this nationwide study of several subsets of SpA, RTX had only a moderate efficacy that was more marked in patients who were anti-TNF-naive.

Objective: To compare the clinical efficacy of certolizumab pegol (CZP) with that of other anticytokine agents indicated for the treatment of rheumatoid arthritis (RA) with identical therapeutic indication (anti-tumor necrosis factor-α, anti-interleukin 1 or 6), with the objective of determining the noninferiority of CZP., Methods: A systematic review was performed to identify randomized controlled trials that assessed the efficacy of anticytokine agents in combination with conventional disease-modifying antirheumatic drugs (DMARD) after 6 months of treatment, using the American College of Rheumatology (ACR) response criteria, in patients with RA who have shown inadequate response to DMARD including methotrexate. Indirect treatment comparisons were carried out by a multiple-treatment Bayesian random-effects metaanalysis. Data were analyzed using the Markov chain Monte Carlo simulation. Noninferiority of CZP was assessed in comparison with a predefined equivalence margin of 5%., Results: Nineteen placebo-controlled studies were identified: 14 evaluated the efficacy of 5 anti-TNF-α agents (infliximab, etanercept, adalimumab, golimumab, CZP) and 5 evaluated efficacy of 2 anti-interleukin agents (anakinra, tocilizumab). Every treatment showed significant efficacy versus placebo in individual studies. The multiple-treatment metaanalysis showed a highest OR for CZP on ACR20 response. Metaanalysis indicates that the efficacy of CZP according to ACR20 response is superior to that of infliximab, adalimumab, and anakinra, and equivalent or superior to that of etanercept, golimumab, and tocilizumab. According to ACR50 response, the efficacy of CZP is equivalent or superior to that of all other anticytokines., Conclusion: Results of this original multiple-treatment Bayesian metaanalysis indicate that certolizumab pegol is at least as efficacious as the preexisting antirheumatic anticytokine biotherapies.

Objective: Muscle involvement is a frequent histopathologic feature of sarcoidosis, but its clinical presentation has been rarely reported and its longterm outcome is unclear. We describe the features and outcome of 5 patients with muscle sarcoidosis., Methods: A retrospective study from hospital charts over the period 1985-2001 in 2 academic rheumatology centers., Results: Muscle involvement was identified in 5 patients (3 women, 2 men) aged 37 to 61 years, out of a cohort of 45 patients with sarcoidosis. No symptomatic muscle involvement was observed in the 20 patients with Lofgren syndrome of our series. Muscle involvement was the initial feature of the disease in 2 patients. Three patients had nodular type and the 2 others the myositic type. Chronic myopathy was not observed. Followup of patients with muscle disease ranged from 30 to 144 months (mean 72.6). Prednisone was used at a starting dose from about 0.33 to 1 mg/kg/day in all patients, then progressively tapered, and was associated with use of hydroxychloroquine (HCQ) in 2 cases. One poorly compliant patient was persistently prescribed 40 mg/day prednisone and HCQ by his general practitioner and was still complaining of diffuse myalgia at the last 30-month followup visit. One patient also receiving HCQ experienced cardiac and renal relapse, leading to transient increase in steroid dosage, but remained symptom-free 3 years after steroid discontinuation. Muscle relapses occurred in the 3 other patients. Muscle symptoms disappeared after readministration of corticosteroids or increase of prednisone dosage. The first patient was symptom-free without any treatment at the last followup visit. The second was still taking 10 mg/day 144 months after disease onset because of steroid-dependent myalgia. The last patient was asymptomatic with 10 mg/day prednisone at the last evaluation., Conclusion: Symptomatic muscle involvement may be an initial feature of chronic, and usually the systemic form of, sarcoidosis. It responds to corticosteroid therapy, but relapse seems to be frequent.

We describe 2 cases of polyarthralgia-arthritis syndrome induced by rifabutin, an effective treatment for infections of Mycobacterium avium intracellulare complex. This syndrome has been reported with doses higher than 1 g per day when rifabutin is given in monotherapy. But our cases were treated with low doses, 300-450 mg per day, in combination with clarithromycin. The plasma concentration of rifabutin has been shown to be increased by clarithromycin, suggesting that co-prescription of clarithromycin could lead to development of rifabutin induced polyarthralgia-arthritis syndrome.

Bone and joint infections due to Haemophilus parainfluenzae are unusual. We describe a case of hematogenous vertebral osteomyelitis caused by this commensal microorganism of nose and oropharynx. Early diagnosis and therapy were possible within a week using sensitive radiologic methods: technetium bone scanning, computed tomography and magnetic resonance imaging.