Upadacitinib in active ankylosing spondylitis: results of the 2-year, double-blind, placebo-controlled SELECT-AXIS 1 study and open-label extension.

Introduction: Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported.

Methods: In SELECT-AXIS 1, patients receiving placebo were switched to upadacitinib 15 mg once daily at week 14 while patients initially randomised to upadacitinib continued their regimen through week 104. Efficacy was assessed using as-observed (AO) and non-responder imputation (NRI).

Value of Remission in Patients with Rheumatoid Arthritis: A Targeted Review.

The treat-to-target strategy, which defines clinical remission as the primary therapeutic goal for rheumatoid arthritis (RA), is a widely recommended treatment approach in clinical guidelines. Achieving remission has been associated with improved clinical outcomes, quality of life, and productivity. These benefits are likely to translate to reduced economic burden in terms of lower healthcare costs and resource utilization.

Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis.

Objectives: Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical.

Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial.

Objective: To evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1-selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX).

Methods: In total, 1,629 RA patients with an inadequate response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week) while continuing to take a stable background dose of MTX. The primary end points were achievement of an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of <2.

Update on biosimilars in rheumatology.

Biologic agents have become indispensable in the management of autoimmune disease particularly rheumatological conditions. The lives of countless individuals have been improved following treatment with these drugs. Unfortunately, their cost prohibits more widespread use around the globe.

Immune reconstitution 20 years after treatment with alemtuzumab in a rheumatoid arthritis cohort: implications for lymphocyte depleting therapies.

Background: Alemtuzumab, an anti-CD52 monoclonal antibody, was administered to patients with RA between 1991 and 1994. We have followed a cohort of recipients since that time and previously reported significant delays in immune reconstitution. Here we report >20 years of follow-up data from this unique cohort.

Tetrahydrobiopterin Supplementation Improves Endothelial Function But Does Not Alter Aortic Stiffness in Patients With Rheumatoid Arthritis.

Background: Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness.

Methods And Results: We conducted 2 randomized, double-blinded, placebo-controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH4 400 mg versus placebo (n=18), and a short-term regimen, composed of a 1-week treatment with BH4 400 mg once daily versus placebo (n=15).

Evaluating the patient with low back pain.

In the UK, low back pain is the most common cause of disability in young adults and every year 6-9% of adults consult their GP about back pain. A thorough history and examination is required to exclude an alternative diagnosis, such as pain arising from the hip or trochanteric bursa and to categorise patients as having: serious spinal pathology, nerve root/radicular pain or non-specific back pain. Inflammatory back pain is often missed, particularly in the early stages when examination may be normal.

A Systematic Review of Factors Associated with Non-Adherence to Treatment for Immune-Mediated Inflammatory Diseases.

Background: Non-adherence impacts negatively on patient health outcomes and has associated economic costs. Understanding drivers of treatment adherence in immune-mediated inflammatory diseases is key for the development of effective strategies to tackle non-adherence.

Objective: To identify factors associated with treatment non-adherence across diseases in three clinical areas: rheumatology, gastroenterology, and dermatology.

Biologic therapy for inflammatory arthritis and latent tuberculosis: real world experience from a high prevalence area in the United Kingdom.

Biologic therapies have resulted in a sea change in the management of inflammatory arthritis; however, a higher risk of opportunistic infection, particularly tuberculosis (TB), is well recognised. This has led to the development of TB screening guidelines. The aim of this study was to investigate the prevalence of latent TB in patients prescribed biologic therapy in an endemic area (prevalence of TB 50/100,000) and to assess the risk of subsequent reactivation.

Refining the Management of Rheumatoid Arthritis: the Benefits of Subcutaneous Tocilizumab.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune condition which affects approximately 1% of the adult population worldwide and is characterized by joint inflammation, with extra-articular features being common. Interleukin 6 (IL-6) is one of the chief pro-inflammatory cytokines found in the joints and sera of patients with RA. Increased levels of IL-6 correlate with inflammation, disease activity, and radiological damage.

Comparison of tocilizumab as monotherapy or with add-on disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and inadequate responses to previous treatments: an open-label study close to clinical practice.

This was an exploratory analysis comparing the safety and efficacy of tocilizumab monotherapy with those of tocilizumab in combination with disease-modifying anti-rheumatic drugs (DMARDs). Data were from a single-arm, nonrandomized, open-label, 24-week study in patients with rheumatoid arthritis in which patients with inadequate responses to DMARDs or tumor necrosis factor-α inhibitors received tocilizumab 8 mg/kg intravenously every 4 weeks plus methotrexate/other DMARD(s) combination therapy. If they were intolerant of methotrexate/other DMARD, patients received tocilizumab monotherapy.

Self-management pivotal in osteoarthritis.

Osteoarthritis is not caused by ageing per se, although prevalence does increase with age, and does not necessarily deteriorate over time. However, with the ageing population the incidence and prevalence of osteoarthritis will continue to rise. Osteoarthritis remains a clinical diagnosis and importantly radiographic changes and joint symptoms may be poorly correlated.

Early recognition improves prognosis in elderly onset RA.

Although commonly diagnosed in the third to fifth decades of life, the incidence and prevalence of RA continue to increase up to the ninth decade. Age at onset is particularly relevant as the presentation may differ in elderly onset RA (EORA) compared with young onset RA (YORA). Patients with EORA frequently report a more acute presentation, especially if positive for rheumatoid factor (RF).

Indispensable or intolerable? Methotrexate in patients with rheumatoid and psoriatic arthritis: a retrospective review of discontinuation rates from a large UK cohort.

Methotrexate (MTX) has become the first-line treatment for rheumatoid (RA) and psoriatic arthritis (PsA); however, few studies have focused on its tolerability. The objective of our analyses was to study RA and PsA patients in whom MTX was discontinued, the reasons for this and the duration of MTX treatment prior to withdrawal. A retrospective electronic database review was undertaken to identify all patients who had received MTX for RA or PsA.

Validation of clinical examination versus magnetic resonance imaging and arthroscopy for the detection of rotator cuff lesions.

Limited evidence exists regarding the validity of clinical examination for the detection of shoulder pathology. We therefore wished to establish the sensitivity, specificity, positive predictive value and negative predictive value of clinical tests and magnetic resonance imaging (MRI) in the diagnosis of rotator cuff disorders against findings at arthroscopy. Using recognised tests for specific shoulder lesions, 117 patients with shoulder symptoms awaiting surgery were examined in a standard manner.

Pulmonary complications of biological therapies in children and adults with rheumatic diseases.

The management of rheumatic conditions, including those occurring in children, has improved dramatically over the last decade following the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDS) into the therapeutic arsenal. The benefits have been realised in multiple aspects of disease including signs and symptoms, bone and cartilage destruction, disability and quality of life. Overall, bDMARDS have an acceptable safety profile in the short to medium term in adults and children, however, that following longer term use remains unclear.

What do we know about juvenile idiopathic arthritis and vitamin D? A systematic literature review and meta-analysis of current evidence.

Over the last decade vitamin D (Vit D) has been the focus of considerable interest as a potential immunomodulator in a variety of conditions including autoimmune disease. Its influence in juvenile idiopathic arthritis (JIA) however is unclear. We therefore wished to clarify a possible link with the currently available evidence.

Same-day or historical ESR for disease activity score measurement: does it matter?

Several guidelines recommended routine use of Disease Activity Score-28 (DAS28) to monitor disease and the response to treatment for rheumatoid arthritis (RA). In practice, it may be appropriate to use historical erythrocyte sedimentation rate (ESR) values in place of same-day ESR, thereby preventing unnecessary delay in adjusting intervention. We asked whether ESR blood samples taken up to 3 months prior to the clinic appointment were adequate to accurately assess RA disease activity using the DAS28.

Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk. This is not fully explained by traditional risk factors, but direct vascular inflammation and aortic stiffening may play a role. We hypothesized that patients with RA exhibit aortic inflammation, which can be reversed with anti-tumor necrosis factor-α therapy and correlates with aortic stiffness reduction.