Liron Caplan

American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid‐induced osteoporosis

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.

Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice

Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice.

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

To provide evidence‐based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).

Prevalence of Vitamin D Insufficiency/Deficiency in Rheumatoid Arthritis and Associations with Disease Severity and Activity

Objective. 25-hydroxy-vitamin D (25-OH-D) insufficiency/deficiency is increasingly prevalent and has been associated with many chronic diseases, including rheumatoid arthritis (RA). Our purpose was to define the prevalence and associations of 25-OH-D insufficiency/deficiency in a cohort of US veterans with RA. Methods. Vitamin D status (25-OH-D) was assessed in patients with RA using radioimmunoassay on banked plasma collected at enrollment. Insufficiency was defined as concentrations < 30 ng/ml and deficiency as < 20 ng/ml. Associations of 25-OH-D insufficiency/deficiency with patient characteristics obtained at enrollment were examined using multivariate logistic regression, adjusting for age, sex, season of enrollment, and race. Results. Patients (850 men, 76% Caucasian) had a mean (SD) age of 64 (SD 11.3) years. The prevalences of 25-OH-D insufficiency and deficiency were 84% and 43%, respectively. After multivariate adjustment, both insufficiency and deficiency were more common with anti-cyclic citrullinated peptide antibody positivity and non-Caucasian race, and in the absence of vitamin D supplementation. 25-OH-D deficiency, but not insufficiency, was independently associated with higher tender joint counts and highly sensitive C-reactive protein levels. Conclusion. In a predominantly elderly, male RA population, 25-OH-D insufficiency was highly prevalent. With the increasing adverse health outcomes associated with hypovitaminosis D, screening and supplementation, particularly among minority, seropositive patients with RA, should be performed routinely.

Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis

The co‐occurrence of rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA‐associated inflammation.

Remission of rheumatoid arthritis in clinical practice: Application of the American College of Rheumatology/European League Against Rheumatism 2011 remission criteria

OBJECTIVE To describe use of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria in clinical practice. METHODS Remission was examined using data on 1,341 patients with RA (91% men) from the US Department of Veterans Affairs RA (VARA) registry (total of 9,700 visits) and 1,153 patients with RA (25.8% men) in a community rheumatology practice (Arthritis and Rheumatology Clinics of Kansas [ARCK]) (total of 6,362 visits). Cross-sectional and cumulative probabilities were studied, and agreement between the various remission criteria was assessed. Aspects of reliability of the criteria were determined using Boolean-based definitions, as well as the Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) scoring methods proposed by the ACR/EULAR joint committee. RESULTS When the 3-variable ACR/EULAR definition of remission recommended for use in community practice (swollen and tender joint counts ≤1, and visual analog scale score for patients global assessment of disease activity ≤1) was applied, cross-sectional remission was 7.5% (95% confidence interval [95% CI] 6.4, 8.7%) for ARCK and 8.9% (95% CI 7.9, 9.9%) for VARA, and cumulative remission (remission at any observation) was 18.0% (for ARCK) and 24.4% (for VARA), over a mean followup of ∼2.2 years. Addition of the erythrocyte sedimentation rate or C-reactive protein level to the criteria set reduced remission to 5.0-6.2%, and use of the CDAI/SDAI increased the proportions to 6.9-10.1%. Moreover, 1.8-4.6% of the patients met remission criteria at ≥2 visits. Agreement between criteria definitions was good, as assessed by kappa statistics and Jaccard coefficients. Among patients in remission, the probability of a remission lasting 2 years was 6.0-14.1%. Among all patients, the probability of a remission lasting 2 years was <3%. Remission status and examination results for each patient varied substantially among physicians, as determined by multilevel analyses. CONCLUSION Cross-sectional remission occurred in 5.0-10.1% of the patients in these cohorts, with cumulative remission being 2-3 times greater; however, long-term remission was rare. Problems with reliability and agreement limit the usefulness of these criteria in the individual patient. However, the criteria can be an effective method for measuring clinical status and treatment effect in groups of patients in the community.

Rheumatoid arthritis treatment and the risk of severe interstitial lung disease

Objectives: Interstitial lung disease (ILD) is an important complication of rheumatoid arthritis (RA) or its treatment, and is associated with substantially increased mortality. Reports have suggested that infliximab with or without azathioprine might lead to rapidly progressive or fatal ILD. We used an RA data bank to assess the associations of treatments for RA and severe ILD. Methods: ILD was identified in hospitalisations and death records in 100 of 17 598 RA patients and studied in relation to RA therapy with Cox regression analyses. Results: The incidence of hospitalisation for ILD (HILD) was 260 per 100 000 patient years. Among those hospitalised for ILD, 27.0% died. In multivariable models of current and past RA treatment, the only current treatment associated with HILD was prednisone: hazard ratio (HR) 2.5 [95% confidence interval (CI) 1.5–4.1]. Among past therapies, prednisone (HR 3.0, 95% CI 1.0–8.9), infliximab (HR 2.1, 95% CI 1.1–3.8), etanercept (HR 1.7, 95% CI 1.0–3.0), and cyclophosphamide (HR 3.7, 95% CI 0.9–15.5) were associated with HILD. Pre‐existing lung problems were identified in 67% of HILD. Only one case of HILD in the 100 hospitalisations suggested a possible temporal relationship between infliximab and HILD. Conclusions: Associations between RA treatment and HILD are confounded by the prescription of treatments for ILD such as prednisone, infliximab, etanercept, and cyclophosphamide. There is no clear pattern of causal association of treatment and ILD, and there is no clear evidence to support a causal relationship between infliximab, azathioprine, and HILD.

TNF-α Antagonist Use and Risk of Hospitalization for Infection in a National Cohort of Veterans With Rheumatoid Arthritis

Medications used to treat rheumatoid arthritis (RA) may confer an increased risk of infection. We conducted a retrospective cohort study of veterans with RA followed in the United States Department of Veterans Affairs health care system from October 1998 through September 2005. Risk of hospitalization for infection associated with tumor necrosis factor (TNF)-&agr; antagonists therapy was measured using an extension of Cox proportional hazards regression, adjusting for demographic characteristics, comorbid illnesses, and other medications used to treat RA.A total of 20,814 patients met inclusion criteria, including 3796 patients who received infliximab, etanercept, or adalimumab. Among the study cohort, 1465 patients (7.0%) were hospitalized at least once for infection. There were 1889 hospitalizations for infection. The most common hospitalized infections were pneumonia, bronchitis, and cellulitis. Age and several comorbid medical conditions were associated with hospitalization for infection. Prednisone (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.88-2.43) and TNF-&agr; antagonist use (HR, 1.24; 95% CI, 1.02-1.50) were associated with hospitalization for infection, while the use of disease-modifying antirheumatic drugs (DMARDs) other than TNF-&agr; antagonists was not. Compared to etanercept, infliximab was associated with risk for hospitalization for infection (HR, 1.51; 95% CI, 1.14-2.00), while adalimumab use was not (HR, 0.95; 95% CI, 0.68-1.33). In all treatment groups, rate of hospitalization for infection was highest in the first 8 months of therapy.We conclude that patients with RA who are treated with TNF-&agr; antagonists are at higher risk for hospitalization for infection than those treated with other DMARDs. Prednisone use is also a risk factor for hospitalization for infection.Abbreviations: CI = confidence interval, DMARD = disease-modifying antirheumatic drug, HFI = hospitalization for infection, HR = hazard ratio, ICD-9-CM = International Classification of Diseases, Version 9, Clinical Modification, NHDS = National Hospital Discharge Survey, RA = rheumatoid arthritis, TNF-&agr; = tumor necrosis factor-&agr;, VA = Veterans Affairs.

Associations of disease activity and treatments with mortality in men with rheumatoid arthritis: results from the VARA registry

OBJECTIVES To examine the all-cause mortality rate and factors associated with mortality in US veteran men with RA. METHODS Men with RA were enrolled and followed until death or censoring. Vital status was ascertained through systematic record review and standardized mortality ratios (SMRs) were calculated using US life tables for men. Multivariate Cox proportional hazards regression was used to examine the independent associations of patient factors including socio-demographics, comorbidity, measures of RA disease activity/severity and medication use with mortality. Measures of RA disease activity and medications were examined as time-varying factors. RESULTS A total of 138 deaths were observed during 2314 patient-years of follow-up (n=1015 patients), corresponding to a crude morality rate of 5.9 deaths per 100 patient-years (95% CI 5.0, 7.0) and an SMR of 2.1 (95% CI 1.8, 2.5). After multivariate adjustment, factors independently associated with higher mortality risk in men with RA included older age, Caucasian race, low body weight, an increased frequency of rheumatology visits, higher ESR and RF concentrations, increased DAS28, subcutaneous nodules and prednisone use. In contrast, MTX use [hazard ratio (HR) 0.63; 95% CI 0.42, 0.96] was associated with ∼40% lower mortality risk. CONCLUSION Mortality rates among US male veterans with RA are more than twice those of age-matched men in the general population. These results suggest that optimizing disease control, particularly with regimens that include MTX and minimize glucocorticoid exposure, could improve long-term survival in this population.

Anti-CCP antibody and rheumatoid factor concentrations predict greater disease activity in men with rheumatoid arthritis

Objective To examine associations of anti-cyclic citrullinated peptide (aCCP) antibody and rheumatoid factor (RF) concentrations with future disease activity in men with rheumatoid arthritis (RA). Methods Outcome measures were examined in male US veterans with RA and included (1) proportion of observations in remission (disease activity score (DAS28) ≤2.6); (2) remission for ≥3 consecutive months; and (3) area under the curve (AUC) for DAS28. The associations of autoantibody concentration (per 100 unit increments) with outcomes were examined using multivariate regression. Results 826 men with RA were included in the analysis; the mean (SD) age was 65 (10.5) years and follow-up was for 2.6 (1.3) years. Most were aCCP (75%) and RF (80%) positive. After multivariate adjustment, aCCP (OR 0.93; 95% CI 0.89 to 0.96) and RF concentrations (OR 0.92; 95% CI 0.90 to 0.94) were associated with a lower odds of remission, a lower proportion of observation in remission (p=0.017 and p=0.002, respectively) and greater AUC DAS28 (p=0.092 and p=0.007, respectively). Among patients with discordant autoantibody status, higher concentrations of both aCCP and RF trended towards an inverse association with remission (OR 0.93; 95% CI 0.83 to 1.05 and OR 0.80; 95% CI 0.59 to 1.10, respectively). Conclusions Higher aCCP concentrations (particularly in RF-positive patients) are associated with increased disease activity in US veterans with RA, indicating that aCCP concentration is predictive of future disease outcomes in men.