Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis.

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest.

The profiling of axial spondyloarthritis patient candidate to a biologic therapy: Consensus from a Delphi-panel of Italian experts.

Objective: The project aimed to collect expert consensus statements for the profiling of patients with axial spondyloarthritis (axSpA) candidate to biologic agents (bDMARDs) treatment, in order to better define the drivers for the best treatment choice.

Methods: The 6 more interesting topics about axSpA patient profiling were identified by the project steering committee and a panel of axSpA Italian experts. A systematic literature review (SLR) was performed for each of the selected topics according to the PICO format.

Switch or swap strategy in rheumatoid arthritis patients failing TNF inhibitors? Results of a modified Italian Expert Consensus.

Objective: To establish evidence-based and experts' opinion filtered statements on the optimal treatment choice between cycling (switch) and changing mode of action strategies (swap) in RA patients failing TNF inhibitors (TNFis).

Methods: The relevant question (switch vs swap) was rephrased into a research question according to the population, intervention, comparison and outcome (PICO) strategy, considering all the available scientific evidence published from the 2013 EULAR set of recommendations up to mid-January 2016. Final statements derived from the retrieved scientific evidence and experts' consensus, with eventual rephrasing through a Delphi method during a national consensus of Italian rheumatologists.

20 years of experience with tumour necrosis factor inhibitors: what have we learned?

TNF inhibitors are biologic DMARDs approved for the treatment of active RA in mid-1990s. They still represent a valuable therapeutic option to control the activity, disability and radiographic progression of the disease. In the context of TNF inhibitors, there are currently several molecules and different administration routes that provide optimal treatment personalization, allowing us to respond to a patient's needs in the best possible way.

Randomized controlled trials and real-world data: differences and similarities to untangle literature data.

Randomized controlled trials (RCTs) represent the gold-standard of medical evidence to assess the efficacy and safety of therapeutic interventions. However, the need to minimize bias and ensure the correct design to explore the study aims often affects the generalizability of results. As a consequence, the evidence derived from the most rigorous research strategy available is not always representative of the real-world settings for which this evidence is ultimately intended.

One year in review 2017: novelties in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic disease characterised by inflammation of the synovial tissue in joints, which can lead to joint destruction. The primary goal of the treatment is to control pain and inflammation, reduce joint damage and disability, and maintain or improve physical function and quality of life. The present review is aimed at providing a critical analysis of the recent literature on the novelties in the treatment of RA, with a particular focus on the most relevant studies published over the last year.

Prevalence of Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease in a cohort of patients treated with TNF-alpha inhibitors.

Background: Treat to target (T2T), aiming at inactive disease (ID), has become the recommended strategy for axial-SpA (ax-SpA). Using the Ankylosing Spondylitis Disease Activity Score (ASDAS), we assessed the prevalence of ID in ax-SpA patients treated with TNFα inhibitors (TNFi).

Methods: A multicentric, cross-sectional study was performed assessing disease activity status (BASDAI and ASDAS) of consecutive patients with ax-SpA on stable treatment with TNFi for at least six months.

Power Doppler ultrasonographic assessment of the joint-draining lymph node complex in rheumatoid arthritis: a prospective, proof-of-concept study on treatment with tumor necrosis factor inhibitors.

Background: Emerging research on the mechanisms of disease chronicity in experimental arthritis has included a new focus on the draining lymph node (LN). Here, we combined clinical-serological analyses and power Doppler ultrasound (PDUS) imaging to delineate noninvasively the reciprocal relationship in vivo between the joint and the draining LN in patients with rheumatoid arthritis (RA).

Methods: Forty consecutive patients refractory to conventional synthetic disease-modifying anti-rheumatic drugs were examined through parallel PDUS of the hand-wrist joints and axillary LNs and compared with 20 healthy subjects.

Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc-positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study.

Objective: Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear.

Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral Routes of Administration.

Unlabelled: Methotrexate (MTX) is still considered the drug of choice in rheumatoid arthritis (RA) management. Comparing subcutaneous (MTX SC) and oral (MTX OR) routes of administration is important to optimize the everyday therapeutic strategy in the real-life setting. This review summarizes scientific evidence currently available on this topic.

Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs.

Hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients undergoing biological therapy is not infrequent. This condition can occur in patients with chronic hepatitis B as well as in patients with resolved HBV infection. Current recommendations are mainly focused on prevention and management strategies of viral reactivation under tumor necrosis factor-α inhibitors or chimeric monoclonal antibody rituximab.

Oral low-dose glucocorticoids should be included in any recommendation for the use of non-biologic and biologic disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis.

At present, growing scientific evidence from the medical literature and expert opinion provides strong consideration for a mandatory role of glucocorticoids (GCs) in the management of rheumatoid arthritis (RA). Earlier application strategies were based on initial high doses, with subsequent tapering schedules, resulting in dose-related side effects. Recent low-dose GC schemes are more feasible in routine care, while providing evidence of clinical, functional and structural efficacy.

The role of low-dose glucocorticoids for rheumatoid arthritis in the biologic era.

In rheumatoid arthritis (RA), low-dose glucocorticoid (GC) therapy has a well-established effect on disease activity. Particularly in early RA, robust evidence demonstrates that GC treatment in association with standard disease-modifying anti-rheumatic drugs (DMARDs) is effective in inducing high remission rates, earlier and more persistently. Despite international recommendations that discourage long-term concomitant GC use, the majority of the clinical trials and observational registries on biologic agents include a high proportion (up to 80%) of patients in treatment with GC.

Drug survival of the first course of anti-TNF agents in patients with rheumatoid arthritis and seronegative spondyloarthritis: analysis from the MonitorNet database.

Objectives: To compare drug survival of different anti-TNF drugs (infliximab, INF, etanercept, ETA, and adalimumab, ADA) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) by analysing data collected from an Italian multicenter observational cohort study.

Methods: All patients with RA or SpA registered in the MonitorNet database who started their first course of anti-TNF therapy were included. Overall drug survival was measured, along with specific reasons of discontinuation (inefficacy or adverse events).

Glucocorticoids in rheumatoid arthritis.

Interest in the numerous benefits of corticosteroid medication in the management of rheumatoid arthritis (RA) goes back to the mid-1950s, and has recently been renewed. The established evidence of their rapid symptomatic effects, along with the growing recognition of their long-lasting disease-modifying properties and preliminary data about their sub-clinical action, led us to reconsider the potential of corticosteroids in the treatment of RA, given their acceptable safety profile, especially when used at low dosages. Over time, several corticosteroid-based therapeutic approaches have been explored in order to optimize their clinical benefits, while limiting the adverse effects.

Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12-month open-label randomised study.

Introduction: In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients.

Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs.

Introduction: Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.

Methods: The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.

Recommendations for the use of biologic therapy from the Italian Society for Rheumatology: off-label use.

The advent of biological agents has provided further opportunities to treat resistant or relapsing rheumatic diseases, with robust data for rheumatoid arthritis and spondyloarthritis coming from randomised controlled trials. However there are data also on other rare inflammatory rheumatic diseases even if the evidence available may be heterogeneous and/or controversial. Another challenging scenario is represented by diseases that are not uncommon, but that may present with multiple manifestations and prove resistant to conventional therapies, thus requiring the use of biological agents.

Subclinical remodelling of draining lymph node structure in early and established rheumatoid arthritis assessed by power Doppler ultrasonography.

Objective: To investigate the suitability of power Doppler ultrasonography (PD-US) for the assessment of lymph node (LN) status in RA, evaluating the existence of structural and dynamic modifications in well-characterized stages of the disease.

Methods: Ten patients with active disease and five patients in clinical remission underwent complete clinical and PD-US examination of hands, wrists, axillary and cervical LNs on the same day. Synovitis and PD were graded 0-3.

Early disease control by low-dose prednisone comedication may affect the quality of remission in patients with early rheumatoid arthritis.

In order to identify rate and stability of remission induced by low-dose prednisone comedication in early rheumatoid arthritis (RA), we evaluated patients with early RA (<1 year) who were randomized to receive (P) or not (non-P) low-dose prednisone in association with step-up disease-modifying antirheumatic drug therapy over 2 years. Prevalence and duration of clinical remission were evaluated in the first and second year. Each treatment group included 105 patients; no significant differences were found at baseline.

Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: power Doppler signal predicts short-term relapse.

Objectives: This study aimed to evaluate the usefulness of a systematic musculoskeletal ultrasonographic (US) assessment in the detection of residual disease activity in patients with early RA who achieved clinical remission.

Methods: We prospectively studied 106 early RA patients receiving conventional DMARDs according to a disease activity score (DAS)-steered therapeutic protocol over a 24-month period. Standard evaluation included clinical, laboratory, functional and systematic (44 joints) US assessment.