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Tuberculosis (TB) still represents an important issue for public health in underdeveloped countries, but the use of antitumor necrosis factor agents (anti-TNF) for the treatment of inflammatory rheumatic disorders has reopened the problem also in countries with low TB incidence, due to the increased risk of TB reactivation in subjects with latent tuberculosis infection (LTBI). Over the last 5 years, several non-anti-TNF-targeted biologics have been licensed for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. We reviewed the epidemiology of TB, the role of different cytokines and of the immune system cells involved in the immune response against TB infection, the methods to detect LTBI, and the risk of TB reactivation in patients exposed to non-anti-TNF-targeted biologics. Given the limited role exerted by the cytokines different from TNF, as expected, data from controlled trials, national registries of biologics, and postmarketing surveillance show that the risk of TB reactivation in patients receiving non-anti-TNF-targeted biologics is negligible, hence raising the question whether the screening procedures for LTBI would be necessary.

Objective: A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the first-line tailored biologic therapy in patient with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA)., Methods: Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictor biomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs., Results: Some variables, including the patients' preference, the indication for anti-TNF monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. Further, evidence of a better cost-effectiveness profile for etanercept (ETN) and biosimilar infliximab (IFX) in RA was found. Any biologic may be employed in absence of choice driving factors in RA. Otherwise, a high infection risk or LTBI positivity drive the choice toward abatacept (ABA), tocilizumab (TCZ), or ETN. TCZ should be the first choice if monotherapy is required. High rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) titers should drive the choice toward TCZ or ABA, while in patients at high CVD risk anti-TNF choice, with preference for ETN, seems appropriate. Presence of anterior uveitis or inflammatory bowel disease drives the choice to monoclonal antibody anti-TNFs (MoAb anti-TNFs). In PsA, ustekinumab (UTK), and to a lesser extent ETN, represents the first choice in patients at high infection and TB risk. Anti-TNFs or UTK choice is guided by skin or articular disease severity, enthesitis, and dactylitis, whereas ETN should be preferred if metabolic syndrome or high CV risk complicate PsA., Conclusion: Taking in account of multiple choice driving variables, first-line biologic therapy may be optimized in patients with RA, SpA, and PsA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Pulmonary disease represents an important extraarticular manifestation of rheumatoid arthritis (RA). While the association of RA and interstitial lung disease is widely acknowledged, obstructive lung disease (OLD) in RA is less well understood. We therefore aimed to assess the incidence, risk factors, and mortality of OLD in patients with RA., Methods: We examined a population-based incident cohort of patients with RA and a comparison cohort of individuals without RA. OLD was defined using a strict composite criterion. Cox proportional hazards models were used to compare OLD incidence between the RA and comparator cohorts to investigate risk factors and to explore the impact of OLD on patient survival., Results: A total of 594 patients with RA and 596 subjects without RA were followed for a mean of 16.3 and 19.4 years, respectively. The lifetime risk of developing OLD was 9.6% for RA patients and 6.2% for subjects without RA (hazard ratio [HR] 1.54, 95% confidence interval [95% CI] 1.01-2.34). The risk of developing OLD was higher among male patients, among current or former smokers, and for individuals with more severe RA. Survival of RA patients diagnosed with OLD was worse compared to those without OLD (HR 2.09, 95% CI 1.47-2.97)., Conclusion: Patients with RA are at higher risk of developing OLD, which is significantly associated with premature mortality. Effective diagnostic and therapeutic strategies to detect and manage OLD in patients with RA may help to improve survival in these patients., (Copyright © 2013 by the American College of Rheumatology.)

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes., (Copyright © 2012 by the American College of Rheumatology.)

Objective: Interstitial lung disease (ILD) has been recognized as an important comorbidity in rheumatoid arthritis (RA). We undertook the current study to assess incidence, predictors, and mortality of RA-associated ILD., Methods: We examined a population-based incidence cohort of patients with RA and a matched cohort of individuals without RA. All subjects were followed up longitudinally. The lifetime risk of ILD was estimated. Cox proportional hazards models were used to compare the incidence of ILD between cohorts, to investigate predictors, and to explore the impact of ILD on survival., Results: Patients with RA (n = 582) and subjects without RA (n = 603) were followed up for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for non-RA subjects. This difference translated into a hazard ratio (HR) of 8.96 (95% confidence interval [95% CI] 4.02-19.94). The risk of developing ILD was higher in RA patients who were older at the time of disease onset, in male patients, and in individuals with more severe RA. The risk of death for RA patients with ILD was 3 times higher than in RA patients without ILD (HR 2.86 [95% CI 1.98-4.12]). Median survival after ILD diagnosis was only 2.6 years. ILD contributed approximately 13% to the excess mortality of RA patients when compared with the general population., Conclusion: Our results emphasize the increased risk of ILD in patients with RA. The devastating impact of ILD on survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality among individuals with RA.

Objective: To systematically review the occurrence of malignancies among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) treated with anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in randomized controlled trials (RCTs), and to report a retrospective personal case series evaluating the frequency of malignancies in patients with RA, PsA, and AS requiring anti-TNF therapy selected with more comprehensive cancer screening procedures compared with patients screened according to previously published procedures., Methods: The primary outcome was the report of frequency of malignancies in RCTs and the latency between the therapy introduction and the occurrence of the neoplasm. A total of 363 consecutive RA, PsA, and AS patients requiring anti-TNF therapy from 2002 to 2006 observed at the Rheumatology Unit in Prato, Italy, underwent extensive cancer screening procedures. An historical controlled group of 73 patients treated between January 1999 and December 2001 underwent the screening procedures accepted for the RCT procedures., Results: Thirty-six RCTs were included for analysis. Malignancies occurred in 60 (0.75%) of 8,015 patients randomized to the active treatment arm and in 21 (0.52%) of 3,991 patients in the placebo arms (P = 0.15). In the personal retrospective case series, 1 study patient (0.27%) and 3 controls (4.1%) developed cancer over the followup period (P = 0.017). Mean +/- SD followup duration was 40.9 +/- 16.7 months in study patients and 50.6 +/- 18.1 months in controls., Conclusion: The results of RCTs and our data showing 26% of malignancies occurring within 12 weeks from enrollment suggest the need for a revision of current cancer screening procedures in RCTs and in clinical practice.

Purpose of Review: To examine the role of lung disease in rheumatoid arthritis from a clinical, epidemiologic, pathophysiologic, and therapeutic perspective., Recent Findings: Lung disease in rheumatoid arthritis is pleomorphic and has a marked adverse impact on the morbidity and premature mortality of patients with this disease. Recent advances in the understanding of the pathophysiology of lung disease associated with rheumatoid arthritis reveal it to be characterized by more active cellular infiltrates of both T cells and B cells, as well as other immunologically active cells, including mast cells, than many of the other forms of interstitial lung disease. Satisfactory treatment is lacking; available biologic response modifiers have been reported to have both beneficial and adverse effects on the lung. Newer approaches targeting cellular immunologic dysfunction including T-cell-directed and B-cell-directed therapies hold the promise of reducing lung damage related to the underlying disease., Summary: Lung disease in rheumatoid arthritis is a heterogeneous and oftentimes serious condition, with a profound impact on patient wellbeing and survival. Advances in the understanding of its etiology and targeted application of available, as well as development of new, more specific therapeutics will be of benefit to patients with rheumatoid arthritis who are suffering from lung disease.