Assessment of Early RA Involves A Long Wait

2011 ◽  
Vol 6 (3) ◽  
pp. 1-4
Author(s):  
SARA FREEMAN
Keyword(s):  
2009 ◽  
Vol 39 (1) ◽  
pp. 24
Author(s):  
SHERRY BOSCHERT
Keyword(s):  
Early Ra ◽  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 54.1-54
Author(s):  
S. Benamar ◽  
C. Lukas ◽  
C. Daien ◽  
C. Gaujoux-Viala ◽  
L. Gossec ◽  
...  

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 589-590
Author(s):  
V. Bykerk ◽  
O. Schieir ◽  
M. F. Valois ◽  
L. Bessette ◽  
G. Boire ◽  
...  

Background:Persistent pain can occur in early RA patients, despite improvement in synovitis and may be due to coexisting non-articular pain (NAP). Though NAP is often attributed to fibromyalgia and widespread NAP, regional NAP syndromes may be more common and under-recognized.Objectives:To describe patterns of NAP, predictors of persistent NAP and impact on outcomes in the first year following early RA diagnosis.Methods:Data were from participants enrolled in the Canadian Early Arthritis Cohort (CATCH) between2017-2019who completed 0,6,12-month evaluations with patient-reported outcomes [PROs] and clinical data available. We used the McGill Body Pain Diagram (BPD) to classify patients as experiencing no NAP, regional (RP:1-2 regions) or widespread NAP (WP:3-5 regions). Multinomial regression was used to identify baseline predictors of persistent RP and WP at 12-months. Multi-adjusted GEE with linear and logit links were used to estimate time-varying associations of NAP patterns with outcomes updated at each time point.Results:Study included 421 participants: 66% were female, with a mean(sd) age 56 (14); 72% were seropositive and 90% were treated with MTX ± csDMARDs as initial therapy. NAP at baseline was common (55%), with majority (62%) reporting regional NAP. NAP prevalence was 33% at 12 months (Figure). Female sex and baseline depressive symptoms were independent predictors of widespread NAP at 12 months while poorer function and lack of early MTX treatment independently predicted regional NAP, at 12 mos. Regional and widespread NAP were associated with lower likelihood of remission in adjusted models that accounted for changes in NAP and remission over time (Table).Figure.Point prevalence of regional and widespread NAP at baseline, 6 and 12 months.Table .Results of Multi-Adjusted GEE Logistic Regression showing Regional and Widespread NAP is associated with a reduced likelihood of achieving Stringent Remission TargetsConclusion:NAP is commonly reported in early RA pts seen in real world settings. Regional NAP was more common than WSP at all time-points, but both NAP patterns were associated lower odds of achieving remission targets by 12 months. These data support considering the role of NAP when assessing RA treatment efficacy during clinical visits and warrant different treatment approaches to reduce symptoms in RA patients receiving target-based care.Disclosure of Interests:Vivian Bykerk: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance)Amgen Canada (CATCH, clinical nurse)Abbvie (CATCH, clinical nurse)Pfizer (CATCH, Registry of biologics, Clinical nurse)Hoffman-LaRoche (CATCH)UCB Canada (CATCH, Clinical nurse)BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT)Janssen (CATCH)Celgene (Clinical nurse)Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Glen Hazlewood: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant of: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion,Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, LillyPharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Diane Tin: None declared, Carter Thorne Consultant of: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Susan J. Bartlett Consultant of: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Speakers bureau: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Marit Stockfelt ◽  
Anna-Carin Lundell ◽  
Merete Lund Hetland ◽  
Mikkel Østergaard ◽  
Till Uhlig ◽  
...  

Abstract Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 598.2-598
Author(s):  
E. Myasoedova ◽  
A. Athreya ◽  
C. S. Crowson ◽  
R. Weinshilboum ◽  
L. Wang ◽  
...  

Background:Methotrexate (MTX) is the most common anchor drug for rheumatoid arthritis (RA), but the risk of missing the opportunity for early effective treatment with alternative medications is substantial given the delayed onset of MTX action and 30-40% inadequate response rate. There is a compelling need to accurately predicting MTX response prior to treatment initiation, which allows for effectively identifying patients at RA onset who are likely to respond to MTX.Objectives:To test the ability of machine learning approaches with clinical and genomic biomarkers to predict MTX response with replications in independent samples.Methods:Age, sex, clinical, serological and genome-wide association study (GWAS) data on patients with early RA of European ancestry from 647 patients (336 recruited in United Kingdom [UK]; 307 recruited across Europe; 70% female; 72% rheumatoid factor [RF] positive; mean age 54 years; mean baseline Disease Activity Score with 28-joint count [DAS28] 5.65) of the PhArmacogenetics of Methotrexate in RA (PAMERA) consortium was used in this study. The genomics data comprised 160 genome-wide significant single nucleotide polymorphisms (SNPs) with p<1×10-5 associated with risk of RA and MTX metabolism. DAS28 score was available at baseline and 3-month follow-up visit. Response to MTX monotherapy at the dose of ≥15 mg/week was defined as good or moderate by the EULAR response criteria at 3 months’ follow up visit. Supervised machine-learning methods were trained with 5-repeats and 10-fold cross-validation using data from PAMERA’s 336 UK patients. Class imbalance (higher % of MTX responders) in training was accounted by using simulated minority oversampling technique. Prediction performance was validated in PAMERA’s 307 European patients (not used in training).Results:Age, sex, RF positivity and baseline DAS28 data predicted MTX response with 58% accuracy of UK and European patients (p = 0.7). However, supervised machine-learning methods that combined demographics, RF positivity, baseline DAS28 and genomic SNPs predicted EULAR response at 3 months with area under the receiver operating curve (AUC) of 0.83 (p = 0.051) in UK patients, and achieved prediction accuracies (fraction of correctly predicted outcomes) of 76.2% (p = 0.054) in the European patients, with sensitivity of 72% and specificity of 77%. The addition of genomic data improved the predictive accuracies of MTX response by 19% and achieved cross-site replication. Baseline DAS28 scores and following SNPs rs12446816, rs13385025, rs113798271, and rs2372536 were among the top predictors of MTX response.Conclusion:Pharmacogenomic biomarkers combined with DAS28 scores predicted MTX response in patients with early RA more reliably than using demographics and DAS28 scores alone. Using pharmacogenomics biomarkers for identification of MTX responders at early stages of RA may help to guide effective RA treatment choices, including timely escalation of RA therapies. Further studies on personalized prediction of response to MTX and other anti-rheumatic treatments are warranted to optimize control of RA disease and improve outcomes in patients with RA.Disclosure of Interests:Elena Myasoedova: None declared, Arjun Athreya: None declared, Cynthia S. Crowson Grant/research support from: Pfizer research grant, Richard Weinshilboum Shareholder of: co-founder and stockholder in OneOme, Liewei Wang: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 515.1-515
Author(s):  
Y. Gorbunova ◽  
T. Popkova ◽  
L. Kondrateva ◽  
M. Cherkasova ◽  
E. Nasonov ◽  
...  

Background:Patients with rheumatoid arthritis (RA) and obesity have a lower risk of early death than patients with normal weight due to the so-called “obesity paradox”. Available publications discuss three phenotypes of obesity: classical obesity, metabolically healthy overweight/obesity, and latent obesity (normal weight associated with metabolic disorders, most importantly - with insulin resistance and adipocytokines imbalance).Objectives:To clarify the prevalence of obesity phenotypes and to identify factors predisposing to «latent obesity» in early RA without diabetes mellitus or hyperglycemia.Methods:The study included 35 pts (23 women, 12 men) with early RA (criteria ACR / EULAR, 2010), 56 [43,0; 60,0] years old, naïve to treatment with glucocorticoids and disease-modifying anti-rheumatics, without established diabetes mellitus. Pts were seropositive for IgM RF and anti-CCP, with highly active RA (DAS28 5,9 [5,2; 6,4]; SDAI 35,4 [27,0; 45,8], and CDAI 31,0 [26,0; 44,0]) scores, and median disease duration of 8.0 [6,0;15.0] months. Electrochemiluminescence assay Elecsys (Roche Diagnostics) was used to measure patients’ insulin levels, and ELISA (DBS – Diagnostics Biochem Canada Inc.) - for evaluation of serum leptin concentrations. Insulin resistance (IR) was defined as Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR) ≥2,77. Leptin levels were considered elevated at values ≥11,1 ng/ml for women, ≥5,6 ng/ml for men. The overweight/obesity status was determined by World Health Organization criteria in pts with body mass index (BMI) ≥25kg/m2.Results:Overweight/obesity were documented in 19 (54, 3%) pts with early RA, 4/19 (21%) had high leptin levels and IR, 11/19 (58%) had isolated hyperleptinemia. Normal BMI was found in 16 (45,7%) pts with early RA, 2/16 (12,5%) had elevated leptin levels and IR, and 6/16 (37,5%) – only hyperleptinemia. Four (21%) out of 19 overweight and 8 (50%) out of 16 pts with normal BMI did not show any metabolic disorders (p=0,02). Сlassical obesity was found in 15 (43%), and latent obesity – in 8 (23%) pts with early RA. Leptin levels correlated with waist circumference (r=0,58, p=0,02), BMI (r=0,71, p=0,0006), ESR (r=0,5, p=0,02) in the overweight/obese pts, and with waist circumference (r=0,59, p=0,03), IgM RF (r=0,58, p=0,03), triglyceride levels (r=0,77, p=0,003), and atherogenic index (r=0,62, p=0,03) in pts with normal weight.Conclusion:The classical obesity phenotype associated with abdominal obesity and inflammation was the most common and prevailing over other phenotypes in early RA. Latent obesity was less common and was associated with an unfavorable lipid profile and accumulation of abdominal fat, therefore increasing the risk of cardiovascular diseases in RA. Metabolically healthy overweight/obesity in early RA was really a rare phenotype.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 464-464
Author(s):  
A. Avdeeva ◽  
M. Cherkasova ◽  
E. Nasonov

Background:Anti-citrullinated proteins antibodies (ACPA) are a broad group of antibodies, including antibodies to citrullinated fibrinogen, antibodies to cyclic citrullinated peptide (anti-CCP), antibodies to modified citrullinated vimentin (anti-MCV), antibodies to citrullinated α-enolase.Objectives:To find a potential relationship between ACPA and disease activity, bone destruction, and ACPAs responses to various therapeutic regimens.Methods:The study included 232 patients (pts) with rheumatoid arthritis (RA); 90 pts (74 women, Me;IQR age 53.0 (38.0–58.5) years had early RA, with mean disease duration 5.0 (4.0–9.0) months, DAS 28 5.3 (4.4–6.1)); 142 pts had advanced stage of the disease (123 women, median age 51.0 (43.0–60.0) years, disease duration 56.0 (24.0–96.0) months, DAS 28 6.2 (5.5–6.8)). Pts with early RA received methotrexate (MTX) subcutaneously at average 17.5 mg dose once weekly. Pts with advanced RA received the following anti-B-cell therapy: 34 pts - rituximab (RTX); 20 pts - RTX biosimilar; 43 pts - tocilizumab (TCZ) in combination with conventional DMARDs. Serum anti-CCP and anti-MCV concentrations were measured using ELISA.Results:77 (85.6%) pts with early RA were high positive for anti-CCP, and 29 (70.7%) pts - high positive for anti-MCV. A positive correlation was found between anti-MCV and DAS 28 (r=0.4, p=0.04). As for advanced RA, 78 (80.4%) pts were high positive for anti-CCP, and 70 (79.5%) - for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r=0.4, p=0.02), as well as CDAI (r=0.4, p=0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0-122.0)) were found in pts high positive for anti-MCV (n=79), compared to low-positive/negative (57.0 (31.0–88.0), respectively, (n=27, p<0.05). anti-MCV levels dropped significantly in pts on RTX and TCZ therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment (Table 1)Conclusion:anti-MCV levels correlated with inflammatory activity and development of bone destruction, and were decreasing in pts on treatment. Anti-CCP was less responsive, showed minor changes during treatment, therefore its’ thorough monitoring was not feasible.Disclosure of Interests:None declared


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