Efficacy and safety of levilimab, a monoclonal antibody to interleukin-6 receptors, in patients with rheumatoid arthritis

Interleukin (IL)-6 is a proinlammatory cytokine contributing significantly to the pathogenesis of joint disease and systemic manifestations of rheumatoid arthritis (RA). Levilimab is a new original monoclonal antibody that blocks both soluble and membrane-bound IL-6 receptors. Efficacy and favorable safety profile of levilimab in combination with methotrexate were shown in two randomized double-blind placebo-controlled trials (AURORA and SOLAR) that included patients with active RA despite treatment with methotrexate alone. Both primary and multiple secondary efficacy endpoints including ACR response, low disease activity or remission rates, changes in RA activity scores, etc, confirmed a higher efficacy of levilimab compared to placebo. Profile of adverse events was typical for IL-inhibitors. Several observational studies suggested that unlike rituximab or medium or high dose glucocorticoids IL-6 receptors inhibitors do not worsen outcomes of COVID19 and do not impair immunogenicity of vaccines against COVID-19. Therefore, patients treated with levilimab should not delay vaccination or modify the dosing regimen prior to vaccination.

AA-amyloidosis in autoinflammatory diseases

AA amyloidosis complicates various chronic inflammatory disorders and is characterized by the accumulation of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. In recent decades, the role of chronic infections and rheumatoid arthritis in the ethiology of AA amyloidosis have decreased significantly as a result of their treatment improvement, whereas both monogenic (familial Meditarranean fever, cryopirin-associated periodic syndrome, etc.) or polygenic (ankylosing spondilitis, psoriatic arthritis, adult onset Still’s disease, etc) autoinflammatory diseases more frequently account for AA-amyloidosis today. Autoinflammatory diseases are a consequence of innate immunity disorders although the latter can contribute to the pathogenesis of autoimmune diseases as well. In patients with autoinflammatory diseases, the suppression of inflammation, even subclinical, is essential to prevent development or progression of AA amyloidosis. The choice of inflammatory agents that can be used to achieve this aim depends on the pathogenesis of autoinflammation, e.g. key mediators that are involved in the activation of inflammatory cascade.

Family genetic screening in rare hereditary diseases

Family genetic testing of probands with newly diagnosed rare hereditary diseases including Fabry disease improves early diagnosis and allows to initiate specific treatment, if available, at earlier stage in affected family members. Diagnosis of Fabry disease, an X-linked lysosomal storage disorder affecting kidneys, heart, brain and other organs, is usually late due to low awareness of physicians about rare diseases. Moreover, early symptoms can be non-specific (e.g. gastrointestinal disorders and autonomic neuropathy) or misleading (e.g. recurrent unexplained fever) whereas characteristic skin rash and keratopathy (cornea verticillata) are frequently overlooked. Undiagnosed patients with Fabry disease can be detected by screening in at-risk populations, such as patients with end-stage renal disease undergoing dialysis or renal transplantation, patients with unexplained left ventricular hypertrophy, and young adults with a history of stroke or transient ischemic attack who have a higher prevalence of the disease compared to general population. High-risk screening paves the way to family screening to identify affected relatives, including children, who can benefit from earlier treatment and genetic counselling. The major barriers to family screening include costs of testing, cultural and societal issues, stigma associated with a diagnosis of genetic disease, low contacts in the family, weak infrastructure, national regulations.

Tolerability and safety of Gam-COVID-Vac (Sputnik V) vaccine in adult patients with autoimmune rheumatic diseases

To evaluate the tolerability and safety profile of GamCOVID-Vak (Sputnik V) vaccine in adult patients with autoimmune inflammatory rheumatic diseases.

Potential clinically significant drug interactions of drugs with fruit and berry juices

Any drug can potentially cause adverse drug reactions (ADRs), including serious and fatal. Some of them are caused by interactions with food, in particular, fruit and berry juices. Juices have a complex chemical composition and each of the chemicals can interact with drugs. Grapefruit juice is one of the most popular and well-studed in terms of potential drug interactions juices. Grapefruit juice is an inhibitor of CYP3A enzymes in the intestine involved in the presystemic metabolism of drug substrates. Therefore, it can increase their absorption. Apple juice at a concentration of 5% significantly reduces the activity of OATP, but not the activity of P-glycoprotein, which, for example, leads to a decrease in AUC and Cmax of fexofenadine to 30- 40% relative to the concentration of fexofenadine in patients drinking only water. Taking 200 ml of grape juice can reduce the concentration of phenacetin in blood plasma and increase the ratio of AUC of paracetamol to phenacetin due to the induction of CYP1A2 activity by grape juice flavonoids or by reducing the rate of absorption of phenacetin. To prevent ADRs, it is recommended to take drugs with water and and not consume simultaneously juices that are known to interact with drugs.

Ankylosing spondylitis: diagnostic challenges and efficacy of upadacitinib

Ankylosing spondilitis (AS) is a relatively common disease mainly affecting young males and presenting with chronic inflammation of the spine and the sacroiliac joints. AS is one of the forms of axial spondyloarthritis (SpA). Diagnosis of AS is usually delayed on average by 8-10 years from the first symptoms. SpA should be considered both in males and females who present with chronic low back pain starting before the age of 45 years and at least one additional factor (inflammatory back pain, HLA-B27, sacroileitis, peripheral arthritis, enthesitis, dactylitis, psoriasis, uveitis, inflammatory bowel disease, family history for SpA, elevated ESR and/or C-reactive protein, and good response to NSAIDs). Such patients should be referred to rheumatologist. MRI improves early diagnosis of AS since it detects inflammatory changes, which precede structural damage of the sacroiliac joints (nonradiographic SpA). Physical exercises and NSAIDs are the first-line treatment for AS, whereas TNF and interleukin-17 inhibitors are widely used as a second-line therapy. Upadacitinib is the first JAK-inhibitor that was approved for the treatment of active AS in adult patients who have responded inadequately to conventional therapy. The authors discuss clinical cases demonstrating efficacy of upadacinitib in patients with AS.

Systemic lupus erythematosus: epidemiology, outcomes and burden

The estimates of incidence and prevalence of systemic lupus erythematosus (SLE) in Europe are 1.5-4.9 per 100 000 persons-years and 30-70 per 100 000 people, respectively. Over the last 50 years, survival in SLE patients has improved significantly. Moreover, immunosuppressive treatment resulted in a decreased risk of death from active disease, whereas infections and cardiovascular disease have become the main causes of death in SLE populations. Almost 70% of SLE patients have recurrent course of disease, although long-term remissions or persistent disease activity also occur in a proportion of patients. Annually, every third SLE patient develops moderately severe or severe flares. Recurrent flares, complications of immunosuppressive treatment and comorbidity are associated with accrual of organ damage that increases the risk of death. SLE patients have impaired health-related quality of life correlating with both disease activity and organ damage. Being on remission of SLE or on low disease activity is associated with better outcomes, including lower mortality and risk of damage or flares, improved quality of life, lower hospitalisation rates and costs. Glucocorticoids remain the mainstay of SLE treatment, although their use should be limited, e.g. by proper administration of immunosuppressive or antiinflammatory agents that have steroid-sparing activity. Treatment and prevention of infections and cardiovascular outcomes are also essential for further improvement of survival of SLE patients.

Elimination of hepatitis C virus in patients on the waiting list for liver transplantation

To study the changes in liver function and portal hypertension, and clinical outcomes after elimination of hepatitis C virus (HCV) by direct-acting antiviral agents in patients awaiting an orthotopic liver transplantation (OLT).

Familial Mediterranean fever: diagnostic issues and treatment options

To evaluate diagnostic and treatment issues in patients with familial Mediterranean fever (FMF) and risk factors for AA-amyloidosis.

Rituximab in systemic sclerosis

To evaluate the effect of intravenous rituximab, a monoclonal antibody to B-cells, on interstitial lung disease, skin fibrosis and arthritis in patients with systemic sclerosis (SSc).