Focus on Filgotinib in Rheumatoid Arthritis: A Trial-Based Review.

Janus kinases (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is involved in pathophysiologic cascade of a notable number of rheumatic diseases. The development of JAK inhibitors has expanded treatment choices in rheumatoid arthritis (RA) with a sustained class-effect efficacy. Filgotinib is a novel selective inhibitor of JAK1 isoform licensed for use in RA and ulcerative colitis. In this review we aim to present an analysis of filgotinib's efficacy and drug-specific safety warnings. Patients with RA with or without concomitant conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) (naïve or experienced) and those who have failed biologic Disease-Modifying Antirheumatic Drugs (bDMARDs) were examined in randomised clinical trials. Filgotinib was also tested against placebo, methotrexate, or adalimumab. Long-term extension trials provide insights for up to four years of continuous filgotinib administration. Beneficial effects are depicted in both disease activity parameters and quality of life indexes in moderate or severe RA with a longitudinal efficacy. In head-to-head comparison with adalimumab, filgotinib 200 mg was non-inferior. Adverse effects alerts are marked by the elevated risk of infectious adverse effects with the exception of herpes zoster infection, which has a low incidence.

Understanding and managing cardiac involvement in systemic sclerosis.

INTRODUCTION: Cardiac involvement is common in systemic sclerosis occurring in up to 80% of patients. Primary myocardial dysfunction results from impairment of coronary microvascular circulation, myocardial inflammation and fibrosis with the prevalence of atherosclerosis remaining contradictory. AREAS COVERED: This review presents the various aspects of cardiac involvement in SSc from a pathophysiological, clinical, diagnostic and therapeutic standpoint. Imaging modalities with emerging role in the understanding of mechanisms and prompt diagnosis of myocardial fibrosis namely cardiac magnetic resonance are also discussed. EXPERT OPINION: Cardiac involvement in SSc - and particularly primary myocardial disease - remains a challenge as clinical symptoms manifest in advanced stages of heart failure and convey poor prognosis. Over the last years the introduction of sophisticated imaging methods of myocardial function has resulted in a better understanding of the underlying pathophysiological processes of myocardial damage such as microvasculopathy, inflammation, diffuse or focal fibrosis. Such developments could contribute to the identification of patients at higher risk for subclinical heart involvement for whom diligent surveillance and prompt initiation of therapy with cardioprotective and/or immunosuppressive drugs coupled with invasive interventions namely radiofrequency ablation, implantable cardioverter-defibrillator when indicated, may improve long-term outcomes.

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses.

BACKGROUND: Interstitial lung disease (ILD) is the most important pulmonary manifestation of connective tissue diseases (CTDs) since it is associated with high morbidity and mortality. However, there is uncertainty on what constitutes the optimal treatment options from a variety of competing interventions. The aim of the overview is to summarize existing evidence of the effectiveness and harm of pharmacological therapies for adults with CTD-ILD. METHODS: A literature search will be conducted in MEDLINE, the Cochrane Database of Systematic Reviews, DARE, the Centre for Reviews and Dissemination Health Technology Assessment database, Epistemonikos.org, KSR Evidence, and PROSPERO. We will search for systematic reviews with or without meta-analysis that examine pharmacological treatment for CTD-ILD. Updated supplemental search will also be undertaken to identify additional randomized controlled trials. The primary outcomes will be changes in lung function measures and adverse events. The methodological quality of the included reviews will be assessed using the AMSTAR 2 tool. The overall quality of the evidence will be evaluated using the GRADE rating. Summarized outcome data extracted from systematic reviews will be described in narrative form or in tables. For each meta-analysis we will estimate the summary effect size by use of random-effects and fixed-effects models with 95% confidence intervals, the between-study heterogeneity expressed by I², and the 95% prediction interval. If feasible, given sufficient data, network meta-analysis will be conducted to combine direct and indirect evidence of class and agent comparisons. DISCUSSION: While many factors are crucial in selecting an appropriate treatment for patients with CTD-ILD, evidence for the efficacy and safety of a drug is essential in guiding this decision. Thus, this overview will aid clinicians in balancing the risks versus benefits of the available therapies by providing high-quality evidence to support informed decision-making and may contribute to future guideline development. SYSTEMATIC REVIEW REGISTRATION: MedRxiv: DOI 10.1101/2022.01.25.22269807 PROSPERO: CRD42022303180.

Cardiovascular Magnetic Resonance Detects Inflammatory Cardiomyopathy in Symptomatic Patients with Inflammatory Joint Diseases and a Normal Routine Workup.

Background. Patients with inflammatory joint diseases (IJD) are more likely to develop cardiovascular disease compared with the general population. We hypothesized that cardiovascular magnetic resonance (CMR) could identify cardiac abnormalities in patients with IJD and atypical symptoms unexplained by routine clinical evaluation. Patients-Methods. A total of 51 consecutive patients with IJD (32 with rheumatoid arthritis, 10 with ankylosing spondylitis, and 9 with psoriatic arthritis) and normal clinical, electrocardiographic and echocardiographic workups, were referred for CMR evaluation due to atypical chest pain, shortness of breath, and/or palpitations. Their CMR findings were compared with those of 40 non-IJD controls who were referred for the same reason. All participants were examined using either a 1.5 T or 3.0 T CMR system. For T1/T2 mapping, comparisons were performed separately for each field strength. Results. Biventricular systolic function was similar between groups. In total, 25 (49%) patients with IJD vs. 0 (0%) controls had replacement-type myocardial fibrosis (p < 0.001). The T2 signal ratio, early/late gadolinium enhancement, and extracellular volume fraction were significantly higher in the IJD group. Native T1 mapping was significantly higher in patients with IJD independent of the MRI field strength (p < 0.001 for both). T2 mapping was significantly higher in patients with IJD compared with controls only in those examined using a 1.5 T MR system­52.0 (50.0, 55.0) vs. 37.0 (33.5, 39.5), p < 0.001. Conclusions. In patients with IJD and a mismatch between cardiac symptoms and routine non-invasive evaluation, CMR uniquely identified a significant proportion of patients with myocardial inflammation. A CMR examination should be considered in patients with IJD in similar clinical settings.

TNF-induced Lupus. A Case-Based Review.

Nowadays, tumor necrosis factor-alpha (TNFα) inhibitors have revolutionised the treatment of inflammatory arthritides by demonstrating efficacy with an acceptable toxicity profile. However, autoimmune phenomena and clinical entities have been reported ranging from an isolated presence of autoantibodies to full-blown autoimmune diseases, including drug-induced lupus (DIL). Case Presentation: A 62-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate and prednisone was treated with adalimumab (ADA). 4 months later, she presented acute cutaneous eruptions after sun exposure, positive ANA (1/640 fine speckled pattern), Ro (SSA) and anti- Smith (Sm) antibodies with no other clinical or laboratory abnormalities. The diagnosis of DIL was made, ADA was discontinued, and she was treated successfully with prednisone plus local calcineurin inhibitors. Conclusion: Thus, we review the literature for cases of DIL development in patients treated with TNFα inhibitors. Rheumatologists should be aware of the possible adverse events and the requirement of careful clinical evaluation and monitoring.

Sodium-glucose Cotransporter 2 Inhibitors: Glucose Lowering Against other Hypoglycemic Agents.

BACKGROUND: The treatment of diabetes remains challenging over the decades, even after the introduction of numerous novel drugs of different classes. Most patients with type 2 diabetes require a combination of multiple agents and eventually the use of insulin. The newest antidiabetic drugs, possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2i). This class has a unique mechanism inhibiting the glucose reabsorption in the proximal tubule of the kidney. OBJECTIVE: The purpose of this review is to critically discuss the beneficial effect of SGLT-2i on glycemic control as monotherapy or in combination with other hypoglycemic agents. METHODS: A systematic review of randomised clinical trials on SGLT-2i vs placebo, other glucoselowering drugs or insulin was performed, and studies assessing glycemic control, mainly expressed through glycated hemoglobin and fasting plasma glucose levels (FPG) were included in the review. Electronic and manual searches on MEDLINE, EMBASE and Cochrane Library were performed. RESULTS: In our review, we mainly focused on dapagliflozin, empaglifozin and canagliflozin. All agents exhibited a sufficient reduction of HbA1c as well as FPG. CONCLUSIONS: SGLT-2i are a reliable second-line therapy of T2DM, since they can be combined safely with metformin, sulfonylures, incretin mimetics, insulin as well as in triple combinations. In many studies, they were prioritised as monotherapy with satisfying effects regarding HbA1c and FPG level reductions.

The potential role of statins in treating liver disease.

INTRODUCTION: Statins are commonly use for the management of dyslipidemia, worldwide. Various studies have demonstrated that statins offer significant reduction in the risk of cardiovascular morbidity and mortality. However, this class of drugs has been implicated in potential liver toxicity, thus has been considered as a 'forbidden-drug' in patients with increased liver enzymes. Areas covered: Studies have shown that statins might offer clinical benefits in the setting of viral hepatitis, progression of cirrhosis, and hepatocellular carcinoma. More importantly, this class of drugs was shown to ameliorate liver histological (in both imaging and biopsy studies) and functional alterations in patients with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. In addition, two large survival studies have demonstrated reduction in the risk for cardiovascular events with statin use in patients with elevated transaminase levels at baseline. Expert commentary: These benefits were of greater extent compared with patients with normal liver function tests at baseline. However, current international guidelines seem to neglect these findings and are not including statins in the management algorithm of patients with non-alcoholic fatty liver disease or steatohepatitis. Future randomized studies providing biopsy-proven benefits will establish the use of statins in the prevention of cardiovascular events and therapeutic algorithm of these patients.

Pyoderma gangrenosum and pyogenic arthritis presenting as severe sepsis in a rheumatoid arthritis patient treated with golimumab.

Rheumatoid arthritis is a systemic autoimmune disease resulting in joint destruction and deformities, but also associated with extraarticular and systemic manifestations. The later devastating conditions, such as the development of rheumatoid vasculitis, are more frequently encountered in seropositive patients and their incidence has been attenuated after the introduction of biologic disease modifying drugs, such as anti-tumor necrosis factor alpha (TNFa) agents, which generally have considerably contributed to the better control and long-term outcomes of the disease. Interestingly, autoimmune syndromes may, rarely, present in patients without a positive history after the initiation of treatment. We present a rare case of a woman with seronegative rheumatoid arthritis who developed pyoderma gangrenosum whistle on treatment with golimumab, a fully humanized anti TNFa antibody. The recording of this as well as analogous paradoxical autoimmune syndromes in association with the individual patient characteristics will render treating physicians aware of potential adverse reactions and assist in the understanding of the cytokine driven pathophysiological mechanisms underlying these disorders.