To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase inhibitors, in rheumatoid arthritis ...(RA).
Randomized controlled trials of tofacitinib (5 and 10 mg twice daily) baricitinib (2 and 4 mg daily), and upadacitinib (15 and 30 mg daily) in RA were identified from MEDLINE, EMBASE, and Cochrane databases through December 11, 2019. Random-effects models were used to estimate pooled mean differences and relative risks (RRs). American College of Rheumatology 20%, Health Assessment Questionnaire-Disability Index, adverse events, risk for infection, venous thromboembolic events, and malignancy were calculated.
Twenty trials with an overall low risk of bias involving 8982 patients were identified. Tofacitinib, baricitinib, and upadacitinib improved RA control as determined by American College of Rheumatology 20% (RR, 2.03; 95% CI, 1.87 to 2.20) and Health Assessment Questionnaire-Disability Index scores (mean differences, -0.31; 95% CI, -0.34 to -0.28) compared with placebo. Adverse events were more frequent with upadacitinib, 30 mg, daily (RR, 1.15; 95% CI, 1.02 to 1.30); upadacitinib, 15 mg, daily (RR, 1.14; 95% CI, 1.02 to 1.27); and baricitinib, 4 mg, daily (RR, 1.13; 95% CI, 1.02 to 1.24). The risk for infection was highest with tofacitinib, 10 mg, twice daily (RR, 2.75; 95% CI, 1.72 to 4.41), followed by upadacitinib, 15 mg, daily (RR, 1.35; 95% CI, 1.14 to 1.60) and baricitinib, 4 mg, daily (RR, 1.28; 95% CI, 1.12 to 1.45). Data for venous thromboembolic events were not available for tofacitinib or baricitinib, but there was no increase in risk with upadacitinib (15 mg daily: RR, 2.34; 95% CI, 0.34 to 15.92).
Tofacitinib, baricitinib, and upadacitinib significantly improve RA control. Head-to-head Janus activated kinase inhibitor clinical trials are needed to further inform decision making.
Rheumatoid arthritis and cardiovascular disease Crowson, Cynthia S., MS; Liao, Katherine P., MD, MPH; Davis, John M., MD ...
The American heart journal,
10/2013, Letnik:
166, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a “natural experiment” ...to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease. Methods A review of current literature on heart disease and RA was conducted. Results Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk. Conclusions Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease.
With the increased understanding of the etiology and pathogenesis of rheumatoid arthritis (RA) in recent decades, the notion of disease prevention has arisen. Contemplation of potential preventive ...strategies must be prefaced by a clear understanding of the rationale for the prevention, as opposed to the treatment, of a disease once established. RA is the most common systemic autoimmune rheumatic disease. The worldwide prevalence is 0.24%, and the lifetime cumulative prevalence approaches 4% in women and 2% in men. RA has severe manifestations leading to chronic pain, impaired quality of life, inability to participate in social and work activities, disability, extra-articular manifestations, and premature mortality. Unfortunately, patients often experience a long duration of symptoms prior to diagnosis, owing to inadequate awareness in the general population, limitations of diagnostic assessments in the early phases of the disease, and a lack of access to rheumatologists globally. Despite the development of novel targeted therapies and substantial improvements in treatment strategies, up to 60% of patients fail to respond adequately to any particular treatment strategy, and 30% of those fail to respond to multiple agents. Therefore, there remains a large proportion of patients who fail to achieve clinical remission and patient-acceptable symptom states. Treatments for RA may be associated with a variety of complications, limiting their sustained usefulness, particularly as related to an increased risk for serious infections. Advancements in therapies have curtailed the previous main driver of mortality, cardiovascular disease, but overall mortality remains elevated in many studies of persons with RA compared to the general population. This commentary reviews the rationale in detail and introduces a clear implication that the ideal strategy would be to develop a means of preventing the onset of clinically apparent joint inflammation among individuals at risk.
Tumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central ...nervous system (CNS) events has been postulated but is poorly understood.
To evaluate whether TNF inhibitor exposure is associated with inflammatory demyelinating and nondemyelinating CNS events in patients with an indication for TNF inhibitor use and to describe the spectrum of those CNS events.
A nested case-control study was conducted using the medical records of patients with autoimmune diseases treated at 3 Mayo Clinic locations (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida) between January 1, 2003, and February 20, 2019. Patients were included if their records reported International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnostic codes for US Food and Drug Administration-approved autoimmune disease indication for TNF inhibitor use (ie, rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, Crohn disease, and ulcerative colitis) and diagnostic codes for inflammatory CNS events of interest. Patients were matched 1:1 with control participants by year of birth, type of autoimmune disease, and sex.
TNF inhibitor exposure data were derived from the medical records along with type of TNF inhibitor, cumulative duration of exposure, and time of exposure.
The main outcome was either inflammatory demyelinating (multiple sclerosis and other diseases such as optic neuritis) or nondemyelinating (meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis) CNS event. Association with TNF inhibitor was evaluated with conditional logistic regression and adjusted for disease duration to determine the odds ratios (ORs) and 95% CIs. Secondary analyses included stratification of outcome by inflammatory demyelinating and nondemyelinating CNS events and by autoimmune disease (rheumatoid arthritis and non-rheumatoid arthritis).
A total of 212 individuals were included: 106 patients with inflammatory CNS events and 106 control participants without such events. Of this total, 136 were female (64%); the median (interquartile range) age at disease onset for patients was 52 (43-62) years. Exposure to TNF inhibitors occurred in 64 patients (60%) and 42 control participants (40%) and was associated with an increased risk of any inflammatory CNS event (adjusted OR, 3.01; 95% CI, 1.55-5.82; P = .001). These results were similar when the outcome was stratified by demyelinating and nondemyelinating CNS events. Secondary analyses found the association was predominantly observed in patients with rheumatoid arthritis (adjusted OR, 4.82; 95% CI, 1.62-14.36; P = .005).
This study found that exposure to TNF inhibitors in patients with autoimmune diseases appeared to be associated with increased risk for inflammatory CNS events. Whether this association represents de novo or exacerbated inflammatory pathways requires further research.
To compare the time from first joint swelling to fulfillment of the American College of Rheumatology/European League Against Rheumatism classification criteria between patients with seropositive and ...seronegative rheumatoid arthritis (RA) and to assess the impact of seronegative status on the time from first joint swelling to initiation of disease-modifying antirheumatic drug (DMARD) therapy and achievement of remission.
Times from first provider-documented joint swelling to fulfillment of the 1987 and 2010 American College of Rheumatology/European League Against Rheumatism criteria and to the clinical diagnosis of RA were measured in a population-based cohort of adults with incident RA between January 1, 2009, and December 31, 2014. Disease characteristics and achievement of remission were compared between seropositive (rheumatoid factor positive and/or anti-citrullinated peptide antibody positive) and seronegative (rheumatoid factor negative/anti-citrullinated peptide antibody negative) patients.
The median time from first joint swelling to fulfillment of the 1987 (48 interquartile range (IQR), 0-300 days vs 2 IQR, 0-45 days; P=.001) and 2010 (14 IQR, 0-196 days vs 0 IQR, 0-29 days; P=.004) classification criteria and the median time from first joint swelling to the clinical diagnosis of RA (187 IQR, 13-503 days vs 11 IQR, 0-76 days; P<.001) were significantly longer in seronegative patients than in seropositive patients. The median time from first joint swelling to first prescribed DMARD therapy was significantly longer in seronegative patients (40 IQR, 5-199 days vs 14 IQR, 0-73 days; P=.01). Patients with seronegative RA were less likely to achieve remission (28% vs 50% at 5 years after fulfillment of the 2010 criteria; P=.007), but there was no difference when the patient global score was removed from the remission definition.
Patients with seronegative RA experienced a delay in diagnosis, according to both the 1987 and 2010 classification criteria, as well as a delay in the initiation of DMARD therapy. Patients with seronegative RA were also less likely to attain remission, suggesting that the window of opportunity for intervention may be more frequently missed in this group.
To assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using ...polarising microscopy of synovial fluid (diagnostic yield).
Diagnostic single-centre study of 40 patients with active gout, and 41 individuals with other types of joint disease. Sensitivity and specificity of DECT for diagnosing gout was calculated against a combined reference standard (polarising and electron microscopy of synovial fluid). To explore the diagnostic yield of DECT scanning, a third cohort was assembled consisting of patients with inflammatory arthritis and risk factors for gout who had negative synovial fluid polarising microscopy results. Among these patients, the proportion of subjects with DECT findings indicating a diagnosis of gout was assessed.
The sensitivity and specificity of DECT for diagnosing gout was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All false negative patients were observed among patients with acute, recent-onset gout. All false positive patients had advanced knee osteoarthritis. DECT in the diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30 patients (46.7%).
DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT has a significant impact on clinical decision making when gout is suspected, but polarising microscopy of synovial fluid fails to demonstrate the presence of MSU crystals.
Objective
To identify the incidence, risk factors, and outcomes of rheumatoid arthritis–associated interstitial lung disease (RA‐ILD) and to assess time trends in the incidence and mortality in ...RA‐ILD.
Methods
We included adult residents of Olmsted County, Minnesota with incident RA between 1999 and 2014. Subjects were followed until death, emigration, or April 30, 2019. ILD was defined as the presence of a radiologist‐defined pattern consistent with ILD on chest computed tomography (CT). When chest CT was absent, the combination of chest radiograph abnormalities compatible with ILD and restrictive pattern on pulmonary function testing was considered consistent with ILD. Potential risk factors included age, sex, smoking, obesity, seropositivity, extraarticular manifestations (EAMs), and medications. For survival analysis, we matched RA‐ILD patients to RA–non‐ILD comparators. The frequency and mortality from clinician‐diagnosed RA‐ILD from 1999 to 2014 was compared against a cohort from 1955 to 1994.
Results
During the 1999–2014 time period, 645 individuals (70% women) had incident RA, were a median age of 55.3 years, and 53% never smoked. Twenty‐two patients had ILD before RA, and 51 (67% women) developed ILD during follow‐up. The 20‐year cumulative incidence of RA‐ILD was 15.3%. Ever‐smoking (hazard ratio HR 1.92), age at RA onset (HR 1.89 per 10‐year increase), and severe EAMs (HR 2.29) were associated with incident RA‐ILD. The RA‐ILD cases had higher mortality than their matched RA comparators (HR 2.42). Incidence of RA‐ILD was non‐significantly lower from 1999 to 2014 than from 1955 to1994, but mortality was improved.
Conclusions
RA‐ILD occurs in nearly 1 in 6 patients with RA within 20 years and is associated with shorter survival. Lack of significant change in RA‐ILD incidence over 6 decades deserves further investigation.
Objective
Rheumatoid arthritis (RA) is postulated to originate at mucosal surfaces, particularly the airway mucosa. To investigate this hypothesis, we determined the association between RA and ...asthma, passive smoke exposure, and age at start of smoking.
Methods
For this case–control study, we identified 1,023 cases of RA (175 incident) within a single‐center biobank population, using a rules‐based algorithm that combined self‐report with 2 diagnostic codes. Exposures were self‐reported on biobank questionnaires. Logistic regression models were used to calculate the association of exposures with RA, adjusting for potential confounders. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.
Results
After adjustment for allergies, urban environment, and passive smoke exposure, asthma was found to be associated with RA in the full cohort (OR 1.28 95% CI 1.04–1.58; P = 0.02) but not the incident RA cohort (OR 1.17 95% CI 0.66–2.06; P = 0.60). History of allergic disease was associated with RA in both the full cohort (OR 1.30 95% CI 1.12–1.51; P < 0.001) and the incident RA cohort (OR 1.61 95% CI 1.11–2.33; P = 0.01), especially food allergy, which was significantly associated with RA in the full cohort (OR 1.38 95% CI 1.08–1.75; P = 0.01) and showed a trend toward significance in the incident RA cohort (OR 1.83 95% CI 0.97–3.45; P = 0.06). Passive smoke exposure at home or work was not associated with RA. Finally, age at start of smoking was not associated with increased odds of developing RA in either the full cohort (OR 1.03 95% CI 1.00–1.06; P = 0.03) or the incident RA cohort (OR 1.00 95% CI 0.92–1.08; P = 0.98).
Conclusion
Asthma and allergies may be associated with increased risk of RA. Passive smoke exposure and early age at start of smoking do not appear to influence risk of RA.
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