A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases

Abstract

ObjectivesInforming an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases.MethodsA systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and observational studies. Meeting abstracts from ACR, EULAR conferences and results on clinicaltrials.gov were taken into consideration.Results187 articles fulfilled the inclusion criteria. Evidence for positive effect of IL-6 inhibition was available in various inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still’s disease, cytokine release syndrome due to chimeric antigen receptor T cell therapy and systemic sclerosis-associated interstitial lung disease. Newcomers like satralizumab and anti-IL-6 ligand antibody siltuximab have expanded therapeutic approaches for Castleman’s disease and neuromyelitis optica, respectively. IL-6 inhibition did not provide therapeutic benefits in psoriatic arthritis, ankylosing spondylitis and certain connective tissue diseases. In COVID-19, tocilizumab (TCZ) has proven to be therapeutic in advanced disease. Safety outcomes did not differ from other bDMARDs, except higher risks of diverticulitis and lower gastrointestinal perforations. Inconsistent results were observed in several studies investigating the risk for infections when comparing TCZ to TNF-inhibitors.ConclusionIL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.

Lupus With Erosive Arthritis: A Singular Joint Phenotype of Lupus or Rhupus?

“…8 In this respect, whereas several preclinical works demonstrated the key role of IL-6 in the pathophysiology of several connective tissue disease, and early studies reported encouraging results with IL-6 inhibitors in these conditions, targeting IL-6-mediated signaling in SLE myositis and primary Sjögren syndrome did not show superiority in clinical responses versus placebo, except for a potentially beneficial effect of tocilizumab on preservation of lung function in systemic sclerosis-associated interstitial lung disease. 9 In the same way, a failure of tocilizumab was also observed in 2 and 8 patients who received this drug in our series of rhupus and RA/systemic sclerosis overlap syndrome, respectively. 5,10 Thus, until sets of biomarkers associated with particular involvement or predictive of treatment response become available, rather than trying to attribute all the manifestations, including EA, to the same disease, it is preferable, in our opinion, to consider overlapping syndromes as real entities for which it is more relevant to propose therapies having shown their effectiveness in both components of the syndrome.…”

“…However, the detection of higher levels of interleukin 6 (IL-6) in the blood of SLE patients with JA does not necessarily mean that IL-6 inhibition will be effective 8 . In this respect, whereas several preclinical works demonstrated the key role of IL-6 in the pathophysiology of several connective tissue disease, and early studies reported encouraging results with IL-6 inhibitors in these conditions, targeting IL-6–mediated signaling in SLE myositis and primary Sjögren syndrome did not show superiority in clinical responses versus placebo, except for a potentially beneficial effect of tocilizumab on preservation of lung function in systemic sclerosis–associated interstitial lung disease 9 . In the same way, a failure of tocilizumab was also observed in 2 and 8 patients who received this drug in our series of rhupus and RA/systemic sclerosis overlap syndrome, respectively 5,10 .…”

Targeting IL-6 Signaling Pathways for Musculoskeletal Disorders Treatment: Risks and Benefits

“…It has been demonstrated to be effective in treating a wide range of inflammatory diseases, particularly musculoskeletal conditions such as rheumatoid arthritis (RA), osteoarthritis (OA), and tendinitis [58,59]. New information, particularly regarding RA, enabled us to improve treatment strategies involving tocilizumab and other agents [60]. A number of new compounds, including olokizumab and sirukumab, that target both the IL-6R and the IL-6 ligands have been shown to be clinically effective in treating rheumatoid arthritis (RA), according to a number of very significant new findings [32].…”

“…The outcomes of the phase III clinical trials involving tocilizumab and sarilumab have not yet been made public and are therefore unclear. This is due to the significant risk of bias that was present in both studies, as well as the absence of a comparator arm in one of the reports [60]. According to research that was conducted and published by Zhang et al in 2020, tocilizumab has the potential to be proposed as an additional medication that is both safe and effective for the prevention of relapses in patients who have neuromyelitis optica spectrum disease (NMOSD).…”

Management of patients with rheumatoid arthritis in real clinical practice: Switching from interleukin 6 receptor inhibitors to interleukin 6 inhibitor (olokizumab)

“…Особый интерес представляет эффективность монотерапии ОКЗ. Известно, что у пациентов, которым не подходит комбинированная терапия ГИБП и БПВП, иИЛ-6 имеют определенные преимущества в качестве монотерапии перед иФНО-α [31]. В то же время до сих пор исследований ОКЗ в режиме монотерапии не проводились.…”