Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

Abstract

The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.

Cytokine-Induced and Stretch-Induced Sphingosine 1-Phosphate Production by Enthesis Cells Could Favor Abnormal Ossification in Spondyloarthritis

“…Moreover, fingolimod is the only US Food and Drug Administration (FDA)‐approved drug to date targeting S1P signaling; notwithstanding, it also possesses numerous other molecular targets . Moving forward, to understand the role of S1P metabolism in bone pathophysiology and closely monitoring the development of S1P signaling‐targeting drugs could be a promising approach for SpA treatment …”

Meditope–Fab interaction: threading the hole

“…Monoclonal antibodies (mAbs) are central components in the diagnosis, imaging and treatment of cancers and autoimmune diseases, among other diseases (Weiner et al, 2012;Baker & Isaacs, 2017). Their broad applicability stems from their high target specificity and desirable pharmacokinetics (Kamath, 2016).…”

An imbalance between regulatory T cells and T helper 17 cells in acetylcholine receptor–positive myasthenia gravis patients

“…Patients refractory to conventional treatments have allowed the investigation of molecules that target the IL23/T H 17 pathway. Monoclonal antibodies that target IL‐17, IL‐17R, IL‐12p40, and IL‐23p19 are now being tested, or have been recently approved, to treat autoimmune diseases such as psoriasis, RA, MS, type 1 diabetes, and Crohn's disease . Secukinumab and ixekinumab, monoclonal antibodies that specifically target IL‐17A, have been approved for the treatment of psoriasis and are in phase III clinical trials for psoriatic arthritis .…”

“…The differentiation of pathogenic T H 17 cells is dependent on IL‐23. Ustekinumab, a fully human monoclonal antibody that targets the p40 subunit of IL‐12 and IL‐23, is now available for patients with psoriasis, psoriatic arthritis, and Crohn's disease . By contrast to the previous monoclonal antibodies, ustekinumab has shown efficiency for Crohn's disease patients .…”