Publications

Risankizumab Improved Health-Related Quality of Life, Fatigue, Pain and Work Productivity in Psoriatic Arthritis: Results Of Keepsake 1

Rheumatology (Oxford) 2022 doi: 10.1093/rheumatology/keac342

Kristensen LE,

Soliman AM,

Papp K,

White D,

Barcomb L,

Lu W,

Eldred A,

Behrens F.

In this study risankizumab treatment resulted in greater improvements in fatigue and pain than placebo. Prior to this finding the study aimed to evaluate the impact of risankizumab on HRQoL and other PROs among patients with active PsA and inadequate response or intolerance to csDMARD-IR in the KEEPsAKE 1 trial.

Keywords:

• IL-23,
• Risankizumab,
• PRO / QoL

Guselkumab provides sustained domain-specific and comprehensive efficacy using composite indices in patients with active psoriatic arthritis

Rheumatology (Oxford) 2022 doi: 10.1093/rheumatology/keac375

Coates LC,

Ritchlin CT,

Gossec L,

Helliwell PS,

Rahman P,

Kollmeier AP,

Xu XL,

Shawi M,

Karyekar CS,

Contré C,

Noël W,

Sheng S,

Wang Y,

Xu S,

Mease PJ

This analysis found that patients with active PsA who receive treatment with guselkumab can achieve robust and sustained low disease activity or remission. In reaching this conclusion investigators sought to evaluate the efficacy of guselkumab for the treatment of active PsA through the use of composite indices.

Keywords:

• IL-23,
• Guselkumab,
• Efficacy

A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition

Rheumatology (Oxford). 2021. Epub ahead of print. doi: 10.1093/rheumatology/keab740.

McInnes IB,

Szekanecz Z,

McGonagle D,

Maksymowych WP,

Pfeil A,

Lippe R,

Song IH,

Lertratanakul A,

Sornasse T,

Biljan A,

Deodhar A

JAK inhibitors are likely to become an important part of the overall treatment paradigm for spondyloarthritis (SpA).Although not fully understood, the pathogenesis of SpA is complex and thought to involve both environmental and genetic factors that together elicit a chronic inflammatory response involving the innate and adaptive immune systems. Several different cytokines, TNF, IL-17A, IL-12/23 and IL-23, which are directly/indirectly affected by JAK molecules, are involved in the pathogenesis o...

Keywords:

• JAK,
• Basic Science,
• Review

Efficacy and safety of continuous risankizumab therapy vs treatment withdrawal in patients with moderate to severe plaque psoriasis: A Phase 3 randomized clinical trial

JAMA Dermatol 2020;156:649–58. doi 10.1001/jamadermatol.2020.0723

Blauvelt A,

Leonardi C,

Gooderham M,

Papp K,

Philipp S,

Wu J,

Igarashi A,

Flack M,

Geng Z,

Wu T,

Camez A,

Williams D,

Langley G

Blauvelt et al. shows superior and sustained efficacy for risankizumab in maintaining skin clearance over time versus placebo upon withdrawal, alongside a favourable safety profile in chronic plaque psoriasis through a phase 3, randomised, double-blind, placebo-controlled study, assessing PASI 90 and sPGA score of 0/1 at Week 16.

Keywords:

• Efficacy,
• IL-23,
• Phase 3,
• Risankizumab,
• Safety

Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): A randomised, double-blind, active-comparator-controlled Phase 3 trial

Lancet 2019;394:576–86. doi: 10.1016/S0140-6736(19)30952-3

Reich K,

Gooderham M,

Thaçi D,

Crowley JJ,

Ryan C,

Krueger JG,

Tsai T-F,

Flack M,

Gu Y,

Williams DA,

Thompson EHZ,

Paul C

Treatment with risankizumab showed significantly greater efficacy over adalimumab in providing substantial skin clearance in patients with moderate-to-severe chronic plaque PsO. This study aimed to assess the safety and efficacy of risankizumab compared with adalimumab in an active-comparator Phase 3 trial.

Keywords:

• Efficacy,
• Risankizumab,
• Safety,
• IL-23

Pathogenetic Insights from the Treatment of Rheumatoid Arthritis

Lancet 2017;389:2328–37 DOI 10.1016/S0140-6736(17)31472-1

McInnes I,

Schett G

This review paper examines the understanding gained from looking at the effects of specific immune interventions in the treatment of RA.The introduction of novel IL-6 agents has provided the ideal opportunity to explore the distinct effect of cytokine inhibition, as opposed to receptor inhibition, at the molecular level. Mechanistic insights into TNF could also be obtained in the future with advanced molecular and informatics approaches, and future biopsy studies will be important to explore the...

Keywords:

• Basic Science,
• Review

Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the Phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial

J Am Acad Dermatol 2017;76:418–31. doi: 10.1016/j.jaad.2016.11.042

Reich K,

Armstrong AW,

Foley P,

Song M,

Wasfi Y,

Randazzo B,

Li S,

Shen YK,

Gordon KB

Patients treated with guselkumab showed an improved and sustained clinical response compared to both adalimumab and placebo, without compromising safety profile. The Phase 3 VOYAGE 2 trial by Reich et al focused on treatment interruption and withdrawal, as well as treatment switching from adalimumab to guselkumab.

Keywords:

• Efficacy,
• Guselkumab,
• IL-23,
• Phase 3,
• Safety,
• Switching

Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation

Nature. 2014;510(7503):157–161.

Riol-Blanco L,

Ordovas-Montanes J,

Perro M,

et al.

The abnormal activation of skin immune cells, such as dermal dendritic cells (DDCs) and interleukin (IL)-17-producing γδ T (γδT17) cells, by IL-23 is known to provoke psoriasis-type inflammation. What is less well known is how peripheral nerves regulate cutaneous immune responses. In this study, IL-23-dependent psoriasis-like inflammation was induced in mice to help determine the precise molecular mechanism of neuroimmune communication in the skin. Findings indicate nocic...

Keywords:

• Preclinical,
• MOA

Cytokine networks—towards new therapies for rheumatoid arthritis

Nature Clinical Practice 2005; 1(1):31-9

McInnes IB,

Liew FY

This review describes cytokines and the cytokine network in chronic inflammatory diseases such as rheumatoid arthritis (RA). It also discusses how therapies that target cytokines may be feasible and efficacious treatments option for RA. Various targets are considered including blockade of tumour necrosis factor (TNF) and interleukin-1 (IL-1), as well as the targeting of cytokines that play a central role in immune regulation and tissue matrix destruction such as IL-6, IL-15, interferon-gamma (IF...

Keywords:

• JAK,
• MOA,
• Review

Cytokines in the pathogenesis of rheumatoid arthritis

Nature Reviews Immunology 2007; 7:429-42

McInnes IB,

Schett G

The imbalance between the activity of pro- and anti-inflammatory cytokines favouring induction of autoimmunity, chronic inflammation and joint damage is well known, but how cytokines are organised within a hierarchical regulatory network and which cytokines are the best targets for clinical intervention is uncertain. This review therefore examines the effector function of cytokines in the immunological processes central to the pathogenesis of rheumatoid arthritis (RA). The paper aims to try and ...

Keywords:

• JAK,
• Basic Science,
• MOA,
• Review