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.