Predictors of unacceptable pain with and without low inflammation over 5 years in early rheumatoid arthritis-an inception cohort study.
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ABSTRACT: Objectives
Pain is a major symptom in patients with rheumatoid arthritis (RA). In early RA, pain is usually due to synovitis, but can also persist despite effective anti-inflammatory treatment. The objective of this study was to investigate the pain course over time and predictors of unacceptable pain and unacceptable pain with low inflammation, in patients with early RA.Methods
An inception cohort of 232 patients with early RA, recruited in 1995-2005, was followed in a structured programme for 5 years. Pain was assessed using a visual analogue scale (VAS; 0-100). Unacceptable pain was defined as VAS pain > 40 based on the patient acceptable symptom state (PASS) and low inflammation as CRP < 10 mg/l. Baseline predictors of unacceptable pain were evaluated using logistic regression analysis.Results
Pain improved significantly during the first 6 months, but then remained basically unchanged. Thirty-four per cent of the patients had unacceptable pain 5 years after inclusion. Baseline predictors of unacceptable pain after 5 years were lower swollen joint counts [odds ratio (OR) 0.71 per standard deviation (95% confidence interval (CI) 0.51-0.99)] and higher VAS for pain and global assessment of disease activity. Unacceptable pain with low inflammation after 5 years was negatively associated with anti-CCP antibodies [OR 0.50 (95% CI 0.22-0.98)].Conclusion
Over one third of the patients had unacceptable pain 5 years after inclusion. Lower swollen joint count was associated with unacceptable pain at 5 years. The results may be explained by the positive effects of treatment on pain related to inflammation. Non-inflammatory long-lasting pain appears to be a greater problem in anti-CCP-negative patients.
SUBMITTER: Eberhard A
PROVIDER: S-EPMC8201925 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo describe the disease course of patients with early arthritis without rheumatoid factor (RF) and anti-citrullinated protein auto-antibodies (ACPA) in an inception cohort. To determine baseline predictors of fulfilling 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) for these patients within 3 years.MethodPatients included in the multicenter ESPOIR cohort were compared at baseline and 3 years by whether they were negative for RF and ACPA ("seronegative") or positive for RF and/or ACPA ("seropositive"). Univariate analysis was used to determine the association between baseline variables in seronegative patients and RA classification. Stepwise multiple logistic regression was used to identify predictors of RA classification within 3 years, estimating odds ratios (ORs).ResultsAmong 354 seronegative patients, 224/340 with available data (65.9%) fulfilled RA classification at baseline and 189/233 (81.1%) at 3 years. As compared with seropositive patients, seronegative patients had lower DAS28 (p = 0.002) and lower modified total Sharp score (mTSS; p = 0.026) at baseline; DAS28 remission was similar (p = 0.634), but radiographic progression rate was lower in seronegative patients (p < 0.001) at 3 years. In seronegative patients, factors predicting RA classification within 3 years were additive (OR = 3.61), bilateral (OR = 2.59) and hand, wrist or forefeet involvement (OR = 3.87); presence of a trigger event (OR = 3.57); pain at rest (OR = 2.76); morning stiffness (OR = 2.62); number of tender joints (OR = 23.73); and mTSS (OR = 2.56).Conclusion"Seronegative" patients have less active disease at baseline and less radiographic progression during follow-up than "seropositive" patients. With inflammatory pain, symmetric involvement of numerous small joints and erosive disease, a classification of RA is likely.
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Project description:BackgroundThe development and application of standardised sets of outcomes to be measured and reported in clinical trials have the potential to increase the efficiency and value of research. One of the most notable of the current outcome sets began nearly 20 years ago: the World Health Organization and International League of Associations for Rheumatology core set of outcomes for rheumatoid arthritis clinical trials, originating from the OMERACT (Outcome Measures in Rheumatology) Initiative. This study assesses the use of this core outcome set by randomised trials in rheumatology.MethodsAn observational review was carried out of 350 randomised trials for the treatment of rheumatoid arthritis identified through The Cochrane Library (up to and including September 2012 issue). Reports of these trials were evaluated to determine whether or not there were trends in the proportion of trials reporting on the full set of core outcomes over time. Researchers who conducted trials after the publication of the core set were contacted to assess their awareness of it and to collect reasons for non-inclusion of the full core set of outcomes in the study.ResultsSince the introduction of the core set of outcomes for rheumatoid arthritis, the consistency of measurement of the core set of outcomes has improved, although variation in the choice of measurement instrument remains. The majority of trialists who responded said that they would consider using the core outcome set in the design of a new trial.ConclusionsThis observational review suggests that a higher percentage of trialists conducting trials in rheumatoid arthritis are now measuring the rheumatoid arthritis core outcome set. Core outcome sets have the potential to improve the evidence base for health care, but consideration must be given to the methods for disseminating their availability amongst the relevant communities.
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Project description:BackgroundClinical trials show intensive treatment to induce remission is effective in patients with highly active rheumatoid arthritis (RA). The TITRATE trial showed that the benefits of intensive treatment also extend to moderately active RA. However, many patients failed to achieve remission or show improvements in pain and fatigue. We investigated whether baseline predictors could identify treatment non-responders.MethodsThe impact of obesity, depression, anxiety and illness perception on RA outcomes, including disease activity, remission, pain and fatigue were determined using a pre-planned secondary analysis of the TITRATE trial data.ResultsBody mass index was associated with disease activity levels and remission: obese patients had a higher overall disease activity and fewer obese patients achieved remission. Intensive management was not associated with increased remission in these patients. Obesity was also associated with increased overall pain and fatigue. Anxiety, depression and health perceptions had no discernible impact on disease activity but were associated with high levels of pain and fatigue. There was a strong association between anxiety and high pain scores; and between depression and high fatigue scores; and health perception was strongly related to both. None of the predictors had an important impact on pain and fatigue reduction in cross-sectional analysis.ConclusionsDisease activity is higher in obese patients and they have fewer remissions over 12 months. Anxiety, depression and health perceptions were associated with higher pain and fatigue scores. Intensive management strategies need to account for these baseline features as they impact significantly on clinical and psychological outcomes.Trial registrationISRCTN 70160382 ; date registered 16 January 2014.
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Project description:IntroductionThe safety of tofacitinib in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in clinical studies of ≤ 4 and 9.5 years, respectively. Post-marketing surveillance (PMS) data for tofacitinib from spontaneous and voluntary adverse event (AE) reports have been published for RA, but not PsA. To inform the real-world safety profile of tofacitinib in PsA, we evaluated AE reports submitted to the Pfizer safety database (including RA data for context).MethodsEndpoints included AEs, serious AEs (SAEs), AEs of special interest (AESIs; serious infections, herpes zoster, cardiovascular events, malignancies, venous thromboembolism), and fatal cases. Exposure was estimated using IQVIA global commercial sales data. Number, frequency, and reporting rates (RRs; number of events/100 patient-years' [PY] exposure) were summarized by indication and formulation (immediate release [IR] 5 or 10 mg twice daily], modified release [MR] 11 mg once daily, or all tofacitinib). The data-collection period differed by indication (PsA: 14 December 2017 [US approval, IR/MR] to 6 November 2021; RA: 6 November 2012 [US approval, IR] to 6 November 2021; MR approval, 24 February 2016).ResultsA total of 73,525 case reports were reviewed (PsA = 5394/RA = 68,131), with 20,706/439,370 PY (PsA/RA) of exposure. More AEs were reported for IR versus MR (IR/MR: PsA = 8349/7602; RA = 137,476/82,153). RRs for AEs (IR/MR: PsA = 59.6/113.4; RA = 44.0/64.8) and SAEs (PsA = 8.1/13.6; RA = 8.0/9.5) were higher with MR versus IR. AE RRs (RA) in the first 4 years after IR approval were 95.9 (IR; 49,439 PY) and 147.0 (MR; 2000 PY). Frequency of SAEs, AESIs, and fatal cases was mostly similar across formulations and indications. The most frequently-reported AE Preferred Terms (PsA/RA) included drug ineffective (20.0%/17.8%), pain (9.7%/10.6%), condition aggravated (9.9%/10.5%), headache (8.8%/7.9%) and, for PsA, off-label use (10.5%/3.4%).ConclusionsTofacitinib PMS safety data from submitted AE reports were consistent between PsA and RA, and aligned with its known safety profile. Exposure data (lower MR versus IR; estimation from commercial sales data), reporting bias, reporter identity, and regional differences in formulation use limit interpretation.
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Project description:OBJECTIVES:To investigate changes in bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) over a 10-year period. METHODS:Consecutive patients with early RA (symptom duration <12 months) were followed according to a structured programme and examined with dual-energy X-ray absorptiometry (DXA) at inclusion and after 2, 5 and 10 years. Mean Z-scores over the study period were estimated using mixed linear effect models. Changes in Z-scores between follow-up visits were analysed using paired T-tests. RESULTS:At inclusion, 220 patients were examined with DXA. At the femoral neck, the mean Z-score over 10 years was -0.33 (95 % CI -0.57 to -0.08) in men and -0.07 (-0.22 to 0.08) in women. Men had significantly lower BMD at the femoral neck than expected by age at inclusion (intercept Z-score value -0.35; 95?% CI -0.61 to -0.09), whereas there was no such difference in women. At the lumbar spine, the mean Z-score over the study period for men was -0.05 (-0.29 to 0.19) and for women 0.06 (-0.10 to 0.21). In paired comparisons of BMD at different follow-up visits, femoral neck Z-scores for men decreased significantly from inclusion to the 5-year follow-up. After 5 years, no further reduction was seen. CONCLUSIONS:In this observational study of a limited sample, men with early RA had reduced femoral neck BMD at diagnosis, with a further significant but marginal decline during the first 5?years. Lumbar spine BMD Z-scores were not reduced in men or women with early RA. Data on 10-year follow-up were limited.
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Project description:ObjectiveTo assess adherence to 3 system-level performance measures in a national early rheumatoid arthritis (RA) cohort.MethodsPatients enrolled in the Canadian Early Arthritis Cohort (2007-2015) who met 1987 or 2010 American College of Rheumatology/European League Against Rheumatism criteria with <1 year of symptom duration and ≥1 year of followup after enrollment were included. Performance measures assessed were the percentage of RA patients seen in yearly followup, and the number of gaps between visits of >12 or >14 months, the percentage of RA patients treated with a disease-modifying antirheumatic drug (DMARD), and days from RA diagnosis to initiation of a DMARD. Results are shown stratified by enrollment year to assess for temporal changes in performance.ResultsA total of 1,763 early RA patients were included (mean age 54 years, 73% female, and 82% white). At enrollment, mean ± SD disease duration was 6 ± 3 months, and Disease Activity Score in 28 joints was 5.1 ± 1.5. Over 8 years, the proportion of patients seen in annual followup declined from 100% to 91%. Over followup, 42% of patients had 0 gaps in care of >12 months, and 64% had 0 gaps >14 months. The percentage of DMARD-treated early RA patients was and remained high (95-87%), and the percentage receiving DMARDs within 14 days of diagnosis was 75%. Median time-to-DMARD therapy was 1 day, indicating DMARDs were initiated at diagnosis (90th percentile 93 days).ConclusionThere was evidence of high adherence to system-level performance measures in this early RA cohort following a protocol. Small declines in performance were noted with increasing length of patient followup. Our findings are useful for performance measure benchmarking.
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Project description:Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months' dietary regimens. A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.
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