Ozanimod as induction therapy and maintenance therapy for ulcerative colitis

N Engl J Med 2021;385:1280–91 doi: 10.1056/NEJMoa2033617

Patients receiving ozanimod displayed a significant improvement in clinical response and all secondary endpoints during both the 10-week induction and 52-week maintenance study periods. Percentage of patients achieving clinical remission at Weeks 10 and 52 was the primary endpoint.

April 2024

Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. Previous bimekizumab Phase 2 clinical studies have shown both rapid and durable clinical improvements in skin clearance, as well as a safety profile in line with expectations from this MoA. This study aimed to evaluate the efficacy and safety of bimekizumab in moderate to severe plaque PsO over 1 year compared with both placebo and ustekinumab.

Bimekizumab versus adalimumab in plaque psoriasis

N Engl J Med 2021; 385:130–41. doi: 10.1056/NEJMoa2102388

Bimekizumab was noninferior and superior to adalimumab with respect to PASI 90 response and IGA score at Week 16. Bimekizumab is a promising IL-17A/F inhibitor that has shown clinical improvement in PsO patients compared to placebo and other IL inhibitors. Warren et al. compared the safety and efficacy of bimekizumab with adalimumab in a 56-week double-blind trial.

June 2021

The JAK/STAT pathway is receiving increasing attention in modulation of nociceptive responses, given its clear role in cytokine signalling. The authors of this review speculate that JAKinibs may have an effect on the modulation of nociception and reduction of pain.Crispino N, et al. review the impact of pain in patients with rheumatic disease and the physiological basis of modulating nociceptive pain. They examine the role of cytokines in the modulation of pain and analyse current clinical JAKin...

April 2021

Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

Front. Cell Dev. Biol. 9:630942 DOI: 10.3389/fcell.2021.630942

Understanding of the B-cell receptor signalling pathway led to the identification of a suitable drug target to addresses autoimmunity and inflammation in areas such as MS, RA, pemphigus and SLE. There are currently 22 BTKis in various stages of clinical development. However, AEs such as cardiovascular and bleeding side effects, as well as rash, diarrhoea and infections have been associated with the inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain.Based on clinic...

Keywords:

JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib

Ann Rheum Dis. 2021 Mar 19:annrheumdis-2020-219012. Epub ahead of print. DOI: 10.1136/annrheumdis-2020-219012

The first study to combine in vitro inhibition of cytokine responses in whole blood with clinical pharmacokinetics of individual JAKinibs to model daily cytokine-mediated pharmacodynamic profiles in healthy individuals and patients with RA, has demonstrated that JAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type.Traves and colleagues have observed that JAKinibs have unique, differential effects on specific cytokine signalling pathways, dependent on cytokine stimulus, ST...