Response to Biologic Drugs in Patients With Rheumatoid Arthritis and Antidrug Antibodies.

Importance: There are conflicting data on the association of antidrug antibodies with response to biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA). Objective: To analyze the association of antidrug antibodies with response to treatment for RA. Design, Setting, and Participants: This cohort study analyzed data from the ABI-RA (Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk of Immunization in Rheumatoid Arthritis Patients) multicentric, open, prospective study of patients with RA from 27 recruiting centers in 4 European countries (France, Italy, the Netherlands, and the UK). Eligible patients were 18 years or older, had RA diagnosis, and were initiating a new bDMARD. Recruitment spanned from March 3, 2014, to June 21, 2016. The study was completed in June 2018, and data were analyzed in June 2022. Exposures: Patients were treated with a new bDMARD: adalimumab, infliximab (grouped as anti-tumor necrosis factor [TNF] monoclonal antibodies [mAbs]), etanercept, tocilizumab, and rituximab according to the choice of the treating physician. Main Outcomes and Measures: The primary outcome was the association of antidrug antibody positivity with EULAR (European Alliance of Associations for Rheumatology; formerly, European League Against Rheumatism) response to treatment at month 12 assessed through univariate logistic regression. The secondary end points were the EULAR response at month 6 and at visits from month 6 to months 15 to 18 using generalized estimating equation models. Detection of antidrug antibody serum levels was performed at months 1, 3, 6, 12, and 15 to 18 using electrochemiluminescence (Meso Scale Discovery) and drug concentration for anti-TNF mAbs, and etanercept in the serum was measured using enzyme-linked immunosorbent assay. Results: Of the 254 patients recruited, 230 (mean [SD] age, 54.3 [13.7] years; 177 females [77.0%]) were analyzed. At month 12, antidrug antibody positivity was 38.2% in patients who were treated with anti-TNF mAbs, 6.1% with etanercept, 50.0% with rituximab, and 20.0% with tocilizumab. There was an inverse association between antidrug antibody positivity (odds ratio [OR], 0.19; 95% CI, 0.09-0.38; P < .001) directed against all biologic drugs and EULAR response at month 12. Analyzing all the visits starting at month 6 using generalized estimating equation models confirmed the inverse association between antidrug antibody positivity and EULAR response (OR, 0.35; 95% CI, 0.18-0.65; P < .001). A similar association was found for tocilizumab alone (OR, 0.18; 95% CI, 0.04-0.83; P = .03). In the multivariable analysis, antidrug antibodies, body mass index, and rheumatoid factor were independently inversely associated with response to treatment. There was a significantly higher drug concentration of anti-TNF mAbs in patients with antidrug antibody-negative vs antidrug antibody-positive status (mean difference, -9.6 [95% CI, -12.4 to -6.9] mg/L; P < 001). Drug concentrations of etanercept (mean difference, 0.70 [95% CI, 0.2-1.2] mg/L; P = .005) and adalimumab (mean difference, 1.8 [95% CI, 0.4-3.2] mg/L; P = .01) were lower in nonresponders vs responders. Methotrexate comedication at baseline was inversely associated with antidrug antibodies (OR, 0.50; 95% CI, 0.25-1.00; P = .05). Conclusions and Relevance: Results of this prospective cohort study suggest an association between antidrug antibodies and nonresponse to bDMARDs in patients with RA. Monitoring antidrug antibodies could be considered in the treatment of these patients, particularly nonresponders to biologic RA drugs.

Impact of a Wearable Activity Tracker on Disease Flares in Spondyloarthritis: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of a wearable activity tracker used to encourage physical activity, on disease flares in patients with spondyloarthritis (SpA). METHODS: This randomized controlled trial involved randomizing 108 patients with SpA into tracker and nontracker groups. The participants were then subjected to assessments of disease activity, performance (6-minute walk test), and quality of life (QOL; 36-item Short Form Health Survey) at the 12th, 24th, and 36th week. The primary outcome was the change in the frequency of flare episodes (categorized as no flare, flare in ≤ 3 days, and flare in > 3 days) between baseline and 12 weeks. RESULTS: The results of the study showed that at the 12th week, the mean change (∆) of the number of flares improved in both groups: -0.32 (95% CI -0.66 to 0.02) and -0.38 (95% CI -0.68 to -0.09) in the tracker and nontracker group, respectively. However, the between-group differences were insignificant (P = 0.87). Performance scores improved in both groups at the 12th, 24th, and 36th week (all P < 0.01). The different dimensions of QOL also improved at the 12th week (P < 0.01). Conversely, moderate flares (P < 0.01) and performance (P < 0.01) improved over time; however, the influence over time of a wearable activity tracker was not significant (P = 0.29 and P = 0.66, respectively). CONCLUSION: The use of a wearable activity tracker did not affect the number of flares, performance, or QOL of patients with SpA. Nevertheless, this study confirmed the benefits of physical activity on flares, disease activity, QOL, and physical performance in patients with SpA. (Move Your Spondyl "Better Live Its Rheumatism With the Physical Activity"; ClinicalTrials.gov: NCT03458026).

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry.

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.

Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients.

BACKGROUND: Gain-of-function mutations in STING1 underlie a type I interferonopathy termed SAVI (STING-associated vasculopathy with onset in infancy). This severe disease is variably characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease (ILD). OBJECTIVE: To describe a cohort of patients with SAVI. METHODS: Assessment of clinical, radiological and immunological data from 21 patients (17 families) was carried out. RESULTS: Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most were symptomatic from infancy, but late onset in adulthood occurred in 1 patient. Systemic inflammation, skin vasculopathy, and ILD were observed in 19, 18, and 21 patients, respectively. Extensive tissue loss occurred in 4 patients. Severity of ILD was highly variable with insidious progression up to end-stage respiratory failure reached at teenage in 6 patients. Lung imaging revealed early fibrotic lesions. Failure to thrive was almost constant, with severe growth failure seen in 4 patients. Seven patients presented polyarthritis, and the phenotype in 1 infant mimicked a combined immunodeficiency. Extended features reminiscent of other interferonopathies were also found, including intracranial calcification, glaucoma and glomerular nephropathy. Increased expression of interferon-stimulated genes and interferon α protein was constant. Autoantibodies were frequently found, in particular rheumatoid factor. Most patients presented with a T-cell defect, with low counts of memory CD8+ cells and impaired T-cell proliferation in response to antigens. Long-term follow-up described in 8 children confirmed the clinical benefit of ruxolitinib in SAVI where the treatment was started early in the disease course, underlying the need for early diagnosis. Tolerance was reasonably good. CONCLUSION: The largest worldwide cohort of SAVI patients yet described, illustrates the core features of the disease and extends the clinical and immunological phenotype to include overlap with other monogenic interferonopathies.

Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium.

BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies.

Predictors of response to viscosupplementation in patients with hip osteoarthritis: results of a prospective, observational, multicentre, open-label, pilot study.

BACKGROUND: To identify predictive factors of response to viscosupplementation (VS) in patients with hip osteoarthritis (HOA). METHODS: Prospective, multicentre, open-label trial, achieved in daily practice conditions. Patients with HOA were treated with a single intra-articular injection of a cross-linked hyaluronic acid combined with mannitol (HAnox-M-XL), using imaging guidance. WOMAC pain and function scores and patient global assessment (PGA) were assessed at baseline and day 90. Improvement, satisfaction and efficacy were self-assessed at day 90. Hip radiographs at baseline were scored using Kellgren-Lawrence grade and Osteoarthritis Research Society International (OARSI) score. Associations between clinical and radiological features and response to VS (pain improvement > 50% at day 90) were assessed in univariate analysis, and then using logistic regression, adjusted for confounding factors. RESULTS: The intent-to-treat (ITT) population included 97 patients (57 females, mean age 63). Ninety completed the follow-up and 80 had full clinical and radiological data. Response to VS was achieved in 47.8% of patients. In univariate analysis, the only clinical outcome statistically and negatively related to response was PGA at baseline (p = 0.047). Radiologically, response to VS was negatively correlated with joint space narrowing (JSN) score (JSN < 2 vs. JSN ≥ 2, p = 0.01) and was related to the patterns of femoral head migration (p = 0.008). In multivariate analysis, only JSN grade (p = 0.03) remained significantly related to a poor response. CONCLUSION: This pilot study, which needs further confirmation by larger scale trials, suggests that radiological features might be of importance for the decision of VS in patients with HOA. TRIAL REGISTRATION NUMBER: ID RCB N°2013-A00165-40. Registered 31 January 2013.

Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial.

IMPORTANCE: One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists. OBJECTIVE: To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. DESIGN, SETTING, AND PARTICIPANTS: A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. INTERVENTIONS: Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections. RESULTS: Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). CONCLUSIONS AND RELEVANCE: Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000441.

Influenza and pneumococcal vaccine coverage in 584 patients taking biological therapy for chronic inflammatory joint: A retrospective study.

OBJECTIVES: To evaluate influenza and pneumococcal vaccine coverage in patients taking biological therapy for chronic inflammatory joint disease and to identify factors associated with the decision to administer these two vaccines. METHODS: Retrospective cross-sectional questionnaire study of a cohort of 584 patients taking biological therapy for chronic inflammatory joint disease (rheumatoid arthritis or spondyloarthritis). We studied the influenza and pneumococcal vaccine coverage rates, information about these vaccines given to patients by the primary-care physician and rheumatologist, and reasons for not administering the vaccines. RESULTS: Overall vaccine coverage rates were 44% for influenza and 62% for pneumococcus. Factors associated with being vaccinated were patient age, previous influenza vaccination, and patient information. Concern about adverse effects and absence of patient information by the primary-care physician and rheumatologist were associated with very low coverage rates. CONCLUSION: This study showed insufficient vaccine coverage rates, particularly against influenza, in a population at high risk because of exposure to biological therapy. Patient information by healthcare professionals about influenza and pneumococcal vaccination has a major impact and should be renewed as often as possible.

Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study).

UNLABELLED: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. OBJECTIVE: The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. METHODS: The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). RESULTS: 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. CONCLUSIONS: Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.

Rituximab treatment for spondyloarthritis. A nationwide series: data from the AIR registry of the French Society of Rheumatology.

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.

Onset of action of etanercept in rheumatoid arthritis based on patient-reported outcomes.

BACKGROUND: Onset of action is considered to be a key characteristic of the treatment of rheumatoid arthritis. The efficacy of TNF blockers is usually evaluated after 2 to 4 weeks of therapy. EULAR-RAID is a valid patient-reported outcome composite index. OBJECTIVES: To evaluate the onset of action of etanercept in rheumatoid arthritis patients according to the EULAR-RAID score. METHODS: An open-label, single-arm (etanercept 50 mg/week), 12-week study was carried out in patients with active rheumatoid arthritis. Patients were asked to fill in the RAID score questionnaire each day for the first 14 days of the study and at the 4-week and 12-week visits. Onset of action was evaluated by considering: a) changes over time of the EULAR-RAID score; b) the percentage of patients achieving an 'acceptable' condition according to the EULAR-RAID score (e.g. a score ≤3.00). RESULTS: Of the 120 screened patients, 108 (female: 75%), age 54±13 years, disease duration 8±7 years) were enrolled. At baseline, patients had active rheumatoid arthritis (DAS: 5.4±0.8; CRP: 18.±30mg/l). Eleven patients dropped out of the study. A statistically significant decrease in the EULAR-RAID score was observed by day 1 of therapy. Kaplan-Meier estimates of the proportion of patients achieving an acceptable RAID score were 29.8 [% 95% C.I. 23.8-X42.6], 50 % [95% C.I. 41-60.9], 51.9% [95% C.I. 43.8-63.7], 56% [95% C.I. 49.5-69.1, after 1, 2, 4 and 12 weeks of therapy respectively. The median time to achieve an acceptable EULAR-RAID score was 14.5 days. CONCLUSIONS: This open-label study suggests that patients can perceive a clinically relevant improvement by the first week of etanercept therapy.

The influence of the definition of patient global assessment in assessment of disease activity according to the Disease Activity Score (DAS28) in rheumatoid arthritis.

OBJECTIVE: Patient global assessment (PGA) is one of the 4 items included in the Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis (RA). We studied the influence of the use of 3 different techniques of PGA on the assessment of disease activity. METHODS: We evaluated 3 different DAS28 according to the technique of PGA in 108 patients with active RA before and after 12 weeks of etanercept therapy. RESULTS: The reliability (intraclass coefficient of correlation) between screening and baseline was very high and similar for the 3 DAS28. The percentage of patients in the different states of disease (from remission to higher disease activity) and the sensitivity to change across the 3 DAS28 scales were very similar. CONCLUSION: The different techniques of collection of PGA to be included in the DAS calculation yield similar results. However, an accepted, unequivocal technique should be encouraged in order to reduce heterogeneity in scoring DAS among patients with RA.

Etanercept compared to intraarticular corticosteroid injection in rheumatoid arthritis: double-blind, randomized pilot study.

OBJECTIVE: To compare etanercept (anti-tumor necrosis factor-α) with intraarticular (IA) corticosteroid injections to treat rheumatoid arthritis (RA). METHODS: Patients with RA who had persistent monoarthritis received etanercept or IA corticosteroid injections. Efficacy was compared at Weeks 4 and 24. RESULTS: Thirty-four patients were included (8 dropped out). Mean age was 58.8 years. No difference between groups was found at Weeks 4 or 24, but both groups showed significant improvement at Weeks 4 and 24 compared to baseline. CONCLUSION: Etanercept and IA steroid injections resulted in significant improvement at Week 4 that persisted to Week 24. There was no significant difference in outcome between the groups.

Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial.

OBJECTIVES: To compare the efficacy over 12 weeks of two different etanercept regimens in treating the skin manifestations of psoriasis in patients who also have psoriatic arthritis and to evaluate efficacy and safety over an additional 12 weeks of open label etanercept treatment. Design Randomised double blind multicentre outpatient study. SETTING: 98 outpatient facilities in Europe, Latin America, and the Asia Pacific region. Participants 752 patients with both psoriasis (evaluated by dermatologists) and psoriatic arthritis (evaluated by rheumatologists). INTERVENTIONS: During the blinded portion of the study, participants were randomised to receive etanercept 50 mg twice weekly (n=379) or 50 mg once weekly (n=373) for 12 weeks by subcutaneous injection. All participants then received open label etanercept 50 mg once weekly for 12 additional weeks, while remaining blinded to the regimen. MAIN OUTCOME MEASURES: The primary efficacy end point was the proportion of participants achieving "clear" or "almost clear" on the physician's global assessment of psoriasis at week 12. Secondary efficacy analyses included psoriasis area and severity index, American College of Rheumatology responses, psoriatic arthritis response criteria, and improvement in joint and tendon disease manifestations. RESULTS: At week 12, 46% (176/379) of participants receiving etanercept 50 mg twice weekly achieved a physician's global assessment of psoriasis of "clear" or "almost clear" compared with 32% (119/373) in the group treated with 50 mg once weekly (P<0.001). In contrast, an equally high percentage of participants in both groups achieved psoriatic arthritis response criteria (77% (284/371) in the twice weekly/once weekly group versus 76% (282/371) in the once weekly/once weekly group). Participants treated with 50 mg twice weekly/once weekly had greater mean reductions from baseline in the psoriasis area and severity index at week 12 compared with those who received 50 mg once weekly/once weekly (71% v 62%, P<0.001), with less difference at week 24 (78% v 74%, P<0.110). Joint and tendon disease manifestations improved from baseline in both groups to a similar extent. No new safety signals were seen in either etanercept treatment group, and no significant difference in the safety profiles was observed. CONCLUSIONS: In participants with active psoriasis and psoriatic arthritis, initial treatment of the psoriasis with etanercept 50 mg twice weekly may allow for more rapid clearance of skin lesions than with 50 mg once weekly. A regimen of 50 mg once weekly seems to be appropriate for treatment of joint and tendon rheumatic symptoms. The choice of regimen should be determined by the clinical needs of the individual patient. TRIAL REGISTRATION: Clinical trials NCT00245960.

Effect of discontinuing TNFalpha antagonist therapy in patients with remission of rheumatoid arthritis.

OBJECTIVE: The objective of this study was to determine the time to relapse after tumor necrosis factor alpha (TNFalpha) antagonist discontinuation in patients with remission of rheumatoid arthritis (RA). METHODS: Among 304 patients taking TNFalpha antagonist therapy for RA, 21 achieved a remission and were taken off the TNFalpha antagonist. Remission was defined as DAS28<2.6 for at least 6 months without nonsteroidal inflammatory drugs or more than 5 mg of prednisone per day but with disease-modifying antirheumatic drug (DMARD) therapy if needed. The same TNFalpha antagonist was restarted in the event of a relapse (DAS28>3.2). RESULTS: The 21 patients had a mean age of 61 years, a mean disease duration of 11.3 years, and a mean remission duration at TNFalpha antagonist discontinuation of 19.2 months. The TNFalpha antagonist was infliximab in 2 patients, adalimumab in 5, and etanercept in 14; and 14 patients were taking a concomitant DMARD. The number of patients still in remission after TNFalpha antagonist discontinuation was 9/20 after 6 months and 5/20 after 12 months. Mean time to relapse was 14.7 weeks. While off TNFalpha antagonist therapy, 3 of the 5 relapse-free patients after 12 months were on DMARD therapy, compared to 11 of the 15 patients who relapsed. Compared to the 15 patients who relapsed, the 5 relapse-free patients had a longer time on TNFalpha antagonist therapy (56 months vs. 35 months, P=0.012) and a longer time in remission on TNFalpha antagonist therapy (35 months vs.14.5 months, P=0.04). The 15 patients who relapsed consistently achieved a remission after resuming TNFalpha antagonist therapy; the remission occurred within 2 months in 13 patients. CONCLUSION: TNFalpha antagonist discontinuation in patients in remission of RA was followed by a relapse within 12 months in 75% of cases. Relapsing patients responded well to resumption of the same TNFalpha antagonist.

Outcome of osteoporotic pelvic fractures: an underestimated severity. Survey of 60 cases.

The aim is to describe the characteristics of osteoporotic pelvic fractures and their outcome. We recorded clinical and biological characteristics of 60 osteoporotic pelvic fractures hospitalized in our Department of Rheumatology and assessed their outcome in 51 cases, using a questionnaire administrated by phone call. In our population, pelvic fractures mainly affected elderly women (81.6% of women, mean age 79 years), presenting, in more than 50% of the cases, a past medical history of osteoporosis, previous fracture and cardiovascular disease. The fractures were triggered by a fall in 89% of the cases and mainly located at the pubic rami (65%). There was a high rate of vitamin D deficiency (80.6%) associated with a secondary hyperparathyroidism (51.6%). Before the pelvic fracture, all patients lived at their personal home and 84.1% were autonomous. During hospitalization, 52.5% of the patients experienced an adverse event, mostly related to urinary tract infection and bedsore. At time to discharge, only 31% directly returned to their own home. At the final assessment (mean delay from the fracture: 29 months), 11 patients were dead (mean delay: 190 days). Among living patients, 74.5% lived at home, 60% required assistance for at least one daily life activity and 18.6% experienced a new fracture. Only 63.2% were still treated for osteoporosis. Osteoporotic pelvic fractures requiring initial hospitalization share most characteristics of hip fracture: elderly people, women predominance, vitamin D insufficiency, fall triggering the fracture, and also the severity assessed by a high morbidity and mortality and loss of autonomy.

Injection of intra-articular sodium hyaluronidate (Sinovial) into the carpometacarpal joint of the thumb (CMC1) in osteoarthritis. A prospective evaluation of efficacy.

OBJECTIVE: To compare the efficacy on pain relief and function of one, two or three injections of intra-articular hyaluronic acid in symptomatic osteoarthritis (OA) of the carpometacarpal joint of the thumb (CMCJ). METHODS: Among subjects with symptomatic OA of the CMCJ of the thumb referred to the Rheumatology Department of Nice, patients free of any joint injection in last 6months with pain visual analogue score (VAS) >40 and with Kellgren and Lawrence score between 2 and 4 were included. Each subject was randomly allocated to receive, at weekly intervals, 1 (group 1) or 2 (group 2) or 3 injections (group 3) of 1ml Sodium Hyaluronidate (Sinovial). Injections were given under imaging control. Sociodemographic characteristics, VAS and functionality (Dreiser Functional Index) were assessed at baseline, at one month and at three months. An intention to treat analysis was performed. RESULTS: Forty two subjects were enrolled in the study. Their mean age was 64.8 (8.0) years, and 90.5% were women. Baseline pain VAS, and mean Dreiser functional index were respectively 57.7 (17.1) and 12.5 (5.8). A repeated measure analysis of variance (ANOVA) model was used to compare the time-course profile of the three treatment groups for VAS and Dreiser index. Due to statistically significant groups-time interaction the analyses were conducted at each evaluation time. No difference was found for VAS at 1 month (p=0.075) and 3 months (p=0.382). Intra group differences between baseline and three months was significant in groups 2 and 3 (p=0.012 and p=0.002). CONCLUSION: No significant differences were found between each group over the study period for pain relief and function. But the intra groups analysis results show that intra-articular sodium hyaluronidate injections into the carpometacarpal joint of the thumb in osteoarthritis can be efficacious on pain and fuctionality. What is now needed is a controlled placebo randomised study with larger samples and longer term follow up of the achieved effects.