Publications

Treatment of axial spondyloarthritis: an update

Nat Rev Rheumatol. 18, 205–216 (2022) 2022 doi: 10.1038/s41584-022-00761-z

Danve A & Deodhar A

In this review Danve and Deodhar report an update on modern axSpa treatment. They found that in the past two decades substantial progress in the diagnosis and management of axSpA has been witnessed. Whilst ASAS classification criteria have enabled earlier diagnosis the increased availability of novel therapies, evolving drug safety data and novel clinical trials have allowed clinicians to rethink the placement and timing of drugs in disease management.

Keywords:

• Review

Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients

J Clin Rheumatol. 2021;27(8):e482–e490

Citera G,

Mysler E,

Madariaga H,

Cardiel MH,

Castañeda O,

Fischer A,

Richette P,

Chartrand S,

Park JK,

Strengholt S,

Rivas JL,

Thorat AV,

Girard T,

Kwok K,

Wang L,

Ponce de Leon D

This post hoc analysis of pooled data from 21 clinical trials in the tofacitinib clinical trial programme highlights the importance of identifying known risk factors of RA-interstitial lung disease (ILD) in clinical practice.Citera, et al. investigated incidence rates of ILD – an extra-articular manifestation of RA – in patients with RA, receiving tofacitinib 5 or 10 mg BID and sort to identify potential risk factors for ILD in these patients....

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Lung / ILD

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study

Ann Rheum Dis. 2021 Apr 27;80(8):1004–13.

Deodhar A,

Sliwinska-Stanczyk P,

Xu H,

Baraliakos X,

Gensler LS,

Fleishaker D,

Wang L,

Wu J,

Menon S,

Wang C,

Dina O,

Fallon L,

Kanik KS,

van der Heijde D.

A Phase 3 study assesses the efficacy and safety of tofacitinib in adults with active AS.Deodhar, et al. found that ASAS20 and ASAS40 response rate significantly increased with tofacitinib 5 mg BID versus placebo at Week 16, with improvements maintained to Week 48.There were no new safety signals detected over the course of the study....

Keywords:

• JAK,
• Tofacitinib,
• Phase 3

Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients

Journal of Clinical Rheumatology, Aug 2020 doi: 10.1097/RHU.0000000000001552.

Citera G,

Mysler E,

Madariaga H,

Cardiel M H,

Castaneda O,

Fischer A,

Richette P,

Chartrand S,

Park J K,

Strengholt S,

Rivas J L,

Thorat A V,

Girard T,

Kwok K,

Wang L

This study highlights the importance of accounting for known risk factors of RA-ILD in clinical practice. Interstitial lung disease (ILD) is an extra-articular manifestation of RA. The post-hoc investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. This post-hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 21 Phase 1-4, and 2 long-term ex...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Lung / ILD

Transaminase Levels and Hepatic Events During Tocilizumab Treatment: Pooled Analysis of Long-Term Clinical Trial Safety Data in Rheumatoid Arthritis

Arthritis Rheumatol. 2017 Sep;69(9):1751-1761. doi: 10.1002/art.40176

Genovese MC,

Kremer JM,

van Vollenhoven RF,

Alten R,

Scali JJ,

Kelman A,

Dimonaco S,

Brockwell L

In this pooled analysis investigating liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab (TCZ) treatment for RA in clinical trials, although transaminase elevations were frequent, rates of hepatic serious AEs remained low. Data were pooled from patients who received ≥1 dose of IV TCZ with or without DMARDs in Phase 3 or 4 clinical trials, long-term extensions, and a pharmacology study.A total of 4171 patients were included in the all-exposure population with...

Keywords:

• IL-6,
• Tocilizumab,
• Safety,
• Phase 3,
• LTE

Janus kinases in immune cell signaling

Immunological Reviews 2009; 228:273-87

Ghoreschi K,

Laurence A,

O'Shea JJ

This review from 2009 describes the Janus Kinases (JAK) that includes JAK1, JAK2, and JAK3, a subgroup of non-receptor protein tyrosine kinases. This protein family has a diverse range of functions including roles in cell growth, survival, development, and differentiation of a variety of cells, and especially immune and haematopoietic cells. Current knowledge of protein structure, regulatory mechanisms, signalling pathways and intracellular interactions for the JAK family is reviewed. The paper ...

Keywords:

• JAK,
• MOA,
• Review

Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes

Best Practice & Research Clinical Rheumatology 2010; 24:513-26

Riese RH,

Krishnaswami S,

Kremer J

This article reviews data from animal and phase 2 clinical studies assessing the immunomodulatory effects and pharmacokinetics of CP-690,550 (now known as tofacitinib), as well as its efficacy and safety in patients with rheumatoid arthritis (RA). In two rodent models of arthritis, CP-690,550 produced dose-dependent decreases in signs of disease activity compared with untreated controls, reductions in histologically assessed inflammation and articular cartilage damage, and statistically signific...

Keywords:

• JAK,
• MOA,
• Review