The role of methotrexate (MTX) for the treatment of spondyloarthritis (SpA) remains uncertain. Aims were to compare MTX and tumor necrosis factor inhibitor (TNFi) persistence in spondyloarthritis ...versus rheumatoid arthritis (RA) and to determine whether concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use is associated with improved TNFi persistence in SpA.
This retrospective cohort study using Optum's deidentified Clinformatics Data Mart Database 2000-2014 identified patients with RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS) without prior biologic use who were initiating MTX or a TNFi. Cox proportional hazards models compared time to medication discontinuation over the next 2 years between patients with RA, PsA, or AS, adjusting for potential confounders. In similar analyses stratified by disease, Cox models were used to assess whether concomitant use of csDMARD was associated with TNFi persistence.
We identified 31,527 MTX initiators (26,708 RA, 2939 PsA, 1880 AS) and 34,651 TNFi initiators (24,134 RA, 6705 PsA, 3812 AS). MTX was discontinued sooner in patients with PsA adjusted HR (aHR) 1.10, 95% CI 1.04-1.16 and AS (aHR 1.23, 1.16-1.31) versus RA, while TNFi were discontinued at similar rates in RA and AS and discontinued later in PsA (aHR 0.93, 0.89-0.97). Concomitant use of MTX (compared to no csDMARD) was associated with lower rates of TNFi discontinuation in RA (aHR 0.85, 0.80-0.89), PsA (aHR 0.81, 0.74-0.89), and AS (aHR 0.79, 0.67-0.93).
MTX discontinuation occurs sooner in patients with PsA and AS versus RA. Concomitant use of MTX with a TNFi, however, is associated with improved TNFi persistence in all 3 diseases.
Low muscle mass relative to fat mass (relative sarcopenia) has been associated with mortality and disability but has not been examined after kidney transplantation. We studied how measures of body ...composition change after receipt of a kidney allograft.
Prospective longitudinal cohort study.
60 kidney transplant recipients, aged 20-60 years, at the University of Pennsylvania.
Kidney transplantation.
Dual-energy x-ray absorptiometry measures of fat mass index (FMI) and appendicular lean mass index (ALMI, representing muscle mass), computed tomography measures of muscle density (low density represents increased intramuscular adipose tissue), dynamometer measures of leg muscle strength, and physical activity. ALMI relative to FMI (ALMFMI) is an established index of relative sarcopenia.
Measures expressed as age, sex, and race-specific z scores for transplant recipients were compared with 327 healthy controls. Regression models were used to identify correlates of change in outcome z scores and compare transplant recipients with controls.
At transplantation, ALMI, ALMIFMI, muscle strength, and muscle density z scores were lower versus controls (all P≤0.001). Transplant recipients received glucocorticoids throughout. The prevalence of obesity increased from 18% to 45%. Although ALMI increased after transplantation (P<0.001) and was comparable with the controls from 6 months onward, gains were outpaced by increases in FMI, resulting in persistent ALMIFMI deficits (mean z score of−0.31 at 24 months; P=0.02 vs controls). Muscle density improved after transplantation despite gains in FMI (P=0.02). Muscle strength relative to ALMI also improved (P=0.04) but remained low compared with controls (P=0.01). Exercise increased in the early months after transplantation (P<0.05) but remained lower than controls (P = 0.02).
Lack of muscle biopsies precluded assessment of muscle histology and metabolism.
The 2-year interval after kidney transplantation was characterized by gains in muscle mass and strength that were outpaced by gains in fat mass, resulting in persistent relative sarcopenia.
Background
This study aimed to determine if greater variability in body mass index (BMI) is associated with declines in physical functioning and incident disability in older adults.
Methods
Included ...were participants from the Health, Aging and Body Composition Study who had semi‐annual BMI data during the first 3 years of follow‐up. Participants were categorized into quintiles of BMI variability, using two methods. The first method used average successive variability, whereas the second method adjusted these values to remove the variability due to net change in BMI over the 3‐year period. Linear regression was used to assess the relationship between the two measures of BMI variability and net changes in BMI, fat mass index, appendicular lean mass index, and Health, Aging and Body Composition Physical Performance Score during the first 3 years of the study. Cox proportional hazard models were used to assess the relationship of BMI variability with the subsequent incidence of new disability, adjusting for confounding factors.
Results
Among 2121 participants, those in the highest BMI variability quintile were more likely to lose both body mass (β: −0.086 95% confidence interval, CI: −0.133, −0.040, P < 0.01) and fat mass (β: −0.059 95% CI: −0.117, −0.002, P = 0.04) and had greater declines in physical performance score (β: −0.094 95% CI: −0.162, −0.026, P < 0.01) compared to participants with the least variability in BMI. Participants with high BMI variability also had higher rates of incident disability (hazard ratio: 1.36 95% CI: 1.07, 1.72, P = 0.01), independent of net BMI change.
Conclusions
BMI variability in older adults is associated with decline in physical performance and incident disability. This relationship cannot be explained by net weight loss alone, supporting it as an independent feature of frailty.
Objective
The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after ...elective hip or knee arthroplasty.
Methods
A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity‐adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI) within 1 year.
Results
Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing <4 weeks versus 8–12 weeks was not associated with an increase in infection within 30 days (propensity‐adjusted odds ratio OR 0.90 95% confidence interval (95% CI) 0.60–1.34). The rate of PJI was 2.9 per 100 person‐years and was not increased in patients with stop timing <4 weeks versus 8–12 weeks (hazard ratio HR 0.98 95% CI 0.52–1.87). Glucocorticoid dosage >10 mg/day was associated with increased risk of 30‐day infection (OR 2.11 95% CI 1.30–3.40) and PJI (HR 2.70 95% CI 1.30–5.60). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection.
Conclusion
Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short‐ or long‐term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk.
To determine if early MRI measures predict X-ray progression at 1 and 2 years in a large RA trial cohort.
This study included 256 methotrexate (MTX)-naïve RA patients from a randomised ...placebo-controlled trial of golimumab (GO-BEFORE). MRIs of wrist and 2nd-5th metacarpophalangeal joints at 0, 12, 24, 52 and 104 weeks were obtained and scored using the RAMRIS system. Multivariable logistic regression examined if baseline and early change (weeks 12/24) in RAMRIS scores independently predicted progression of the van der Heijde-Sharp (vdHS) score and MRI erosion score at 1 and 2 years of follow-up.
High baseline score and poor improvement over the first 24 weeks in synovitis (p=0.003 and p=0.003, respectively) and in bone oedema (p=0.02 and p=0.001, respectively) were independent predictors of X-ray progression at 1 year. Associations were significant or tended towards an association at 2 years. An increase in RAMRIS bone erosion >0.5 at weeks 12 and 24 also predicted X-ray progression (p<0.003). Poor 12-week improvement in bone oedema was associated with X-ray and MRI progression at 1 year (p<0.05). Regression models that incorporated baseline and 12-week and 24-week changes in MRI measures of synovitis (AUC=0.71) and bone oedema (AUC=0.70) improved the prediction of X-ray progression at 1 year above clinical disease activity alone (AUC=0.66, p<0.04).
Baseline and early changes in MRI measures independently predicted X-ray and MRI progression at later time-points. The predictive validity established here supports potential use in shorter-duration studies to determine efficacy of RA therapies in preventing structural damage.
Objective
In contrast to what is observed in the general population, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA). The aim of ...this study was to assess whether weight loss might explain these seemingly paradoxical observations.
Methods
Our study included patients identified from the Veterans Affairs (VA) RA Registry. Dates of death were ed from VA electronic medical records. The BMI at each study visit and the change from the previous visit were determined. The maximum BMI of each patient was also obtained from medical records. The annualized rate of BMI loss was determined from the slope of change (per year) in BMI over visits within the preceding 13 months. Cox multivariable proportional hazards models were used to assess associations between BMI measures and mortality.
Results
In a sample of 1,674 patients, 312 deaths occurred over 9,183 person‐years. A loss in BMI of ≥1 kg/m2 was associated with a greater risk of death, after adjustment for demographics, comorbidities, BMI, smoking, and RA therapies (hazard ratio HR 1.99, 95% confidence interval 95% CI 1.53–2.59, P < 0.001). This association remained significant in a subsample analysis adjusting for C‐reactive protein and physical function (HR 1.81, 95% CI 1.36–2.41, P < 0.001). Weight loss at an annualized rate of ≥3 kg/m2 was associated with the greatest risk of death (HR 2.49, 95% CI 1.73–3.57, P < 0.001). Low BMI (<20 kg/m2) in patients with a history of obesity (>30 kg/m2) was associated with the greatest risk (HR 8.52, 95% CI 4.10–17.71, P < 0.001).
Conclusion
Weight loss is a strong predictor of death in patients with RA. These observations may explain the observed obesity paradox and do not support a biologically protective role of obesity.
Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity.
This ...study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity.
At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients.
Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures.
NCT00361335 and NCT00264550; Post-results.
Cyclooxygenase-2 (COX-2) has been found to be important for fracture-healing in animal models, raising concerns about use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 ...inhibitors after fractures. We evaluated associations of NSAIDs, COX-2 inhibitors, and opioids with nonunion after long-bone fracture.
Using private health insurance claims data from Optum's de-identified Clinformatics Data Mart database from January 1, 2000, to September 30, 2015, we identified adults with a single long-bone fracture or commonly paired long-bone fractures who had 1 year of available follow-up data. Using multivariable logistic regression models, we examined associations between NSAID, COX-2-inhibitor, or opioid prescription fills after the fracture and the risk of nonunion within 1 year, defined as a nonunion diagnosis with a procedure to treat the nonunion.
A nonunion diagnosis with a procedure to treat the nonunion was identified after 2,996 (0.9%) of the 339,864 fracture episodes, with rates varying by fracture site. The risk of that outcome was greater in patients who had filled COX-2-inhibitor prescriptions (adjusted odds ratio = 1.84 95% confidence interval = 1.38 to 2.46) or opioid prescriptions (1.69 1.53 to 1.86), but not in patients who had filled nonselective-NSAID prescriptions (1.07 0.93 to 1.23) after the fracture. Results were similar when the outcome definition was changed to just a nonunion diagnosis.
COX-2 inhibitors, but not nonselective NSAIDs, were associated with a greater risk of nonunion after fracture. Opioids were also associated with nonunion risk, although patients filling prescriptions for opioids may have had more severe fractures.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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