Publications

The effect of secukinumab on patient-reported outcomes in patients with active psoriatic arthritis in a randomised phase 3 trial

Lancet. 2022. Epub ahead of print

Strand V,

Kaeley GS,

Bergman MJ,

Gladman DD,

Coates LC,

Sherif B,

Hur P,

Parikh B,

Gilloteau I,

Mease PJ

Predefined analysis of FUTURE 5, the largest Phase 3 randomised trial of secukinumab in patients with PsA to date, demonstrates that secukinumab results in early, statistically significant, clinically meaningful, sustained improvements in PROs across all doses, compared with placebo.The fully human anti-interleukin 17A monoclonal antibody, secukinumab has shown clinical and radiographical efficacy in patients with PsA, yet the clinical significance of improvements across a wide variety of PROs r...

Keywords:

• IL-17,
• Secukinumab,
• PRO / QoL,
• Phase 3

Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis

Ann Rheum Dis. 2022. Epub ahead of print doi: 10.1136/annrheumdis-2021-221323

Lopez-Romero P,

de la Torre I,

Haladyj E,

Aletaha D,

Smolen JS

Baricitinib reduces structural damage progression versus placebo with background MTX and/or MTX, even in patients with moderate or high disease activity.In patients with RA, TNFi, IL-6i and rituximab have been shown to uncouple the link between disease activity and radiographic progression such that patients are protected from structural damage progression even if remission/low disease activity is not achieved.As such, Lopez-Romero, et al. aimed to evaluate if baricitinib further enhances diseas...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Radiographic

Tofacitinib and risk of cardiovascular outcomes: results from the Safety of Tofacitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study

Ann Rheum Dis. 2022 Jan 13. Epub ahead of print doi: 10.1136/annrheumdis-2021-221915

Khosrow-Khavar F,

Kim SC,

Lee H,

Lee SB,

Desai RJ

Real-world evidence finds no increased risk of CV outcomes with tofacitinib, in comparison with TNFi, in patients with RA. However, an elevated risk of CV outcomes cannot be ruled out in patients with CV risk factors or history of CVD.Recent post-marketing findings from the ‘ORAL Surveillance’ trial have raised concerns that tofacitinib, in comparison with TNFi, may increase the risk of CV disease in patients with RA who are at least 50 years of age and with at least one risk factor for CVD. To ...

Keywords:

• JAK,
• Tofacitinib,
• Real-World,
• Cardiovascular

Cardiovascular and Cancer Risk With Tofacitinib in Rheumatoid Arthritis

N Engl J Med 2022;386:316–26. doi: 10.1056/NEJMc2202778

Ytterberg SR,

Bhatt DL,

Mikuls TR,

Koch GG,

Fleischmann R,

Rivas JL,

Germino R,

Menon S,

Sun Y,

Wang C,

Shapiro AB,

Kanik KS,

Connell CA

In this paper, Ytterberg et al. compare incidence of MACE and cancers (excluding NMSC) with tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi. They found that risk of MACE and cancer were higher with tofacitinib versus TNFi, and did not meet noninferiority criteria.This prospective head-to-head safety trial compared tofacitinib to TNFi, and was required by the FDA after increases in lipid levels and cancers were observed during tofacitinib drug development. ...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Malignancy,
• Cardiovascular

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

Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register

Ann Rheum Dis. 2021 Jul 28:annrheumdis-2021-220651

Redeker I,

Albrecht K,

Kekow J,

Burmester GR,

Braun J,

Schäfer M,

Zink A,

Strangfeld A

A 3.6-fold increased risk of herpes zoster (HZ) is associated with tsDMARDs, and an increased risk is associated with bDMARDs, compared with csDMARDs. It is now well known that patients with RA have an increased risk of developing herpes zoster (HZ), and that incidence rates appear to be increased with TNF and JAK inhibitors. To this end, Redeker, et al. used data from the German RABBIT Registry to compare event and incidence rates of HZ in patients with RA treated with the three different DMAR...

Keywords:

• Safety,
• Infections,
• Review

Contribution of a European-Prevalent Variant Near CD83 and an East Asian-Prevalent Variant Near IL17RB to Herpes Zoster Risk in Tofacitinib Treatment: Results of Genome-Wide Association Study Meta-Analyses

Arthritis Rheumatol. 2021;73(7):1155–66

Bing N,

Zhou H,

Chen X,

Hirose T,

Kochi Y,

Tsuchida Y,

Ishigaki K,

Sumitomo S,

Fujio K,

Zhang B,

Valdez H,

Vincent MS,

Martin D,

Clark JD.

Genetic analysis of tofacitinib-treated subjects with RA or PsO identified multiple loci associated with increased herpes zoster (HZ) risk.It is well known that HZ risk is elevated in subjects with RA compared with the general population, and that treatment with JAK inhibitors may result in increased risks compared with TNFi and other bDMARD treatments. To this end, Bing, et al. used genome-wide association studies to identify genetic factors associated with an increased risk/faster onset of HZ ...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry

Ann Rheum Dis. 2021 May 28. DOI: 10.1136/annrheumdis-2021-220418

Sparks JA,

Wallace ZS,

Seet AM,

Gianfrancesco MA,

Izadi Z,

Hyrich KL,

et al.

Results from the COVID-19 Global Rheumatology Alliance physician registry show that people with RA using rituximab or JAKi, at COVID-19 onset, are more likely to experience poor COVID-19 outcomes, ranging from hospitalisation to death, compared with use of TNFi.The ongoing COVID-19 pandemic has had a significant impact on people with RA, many of whom are treated with b/tsDMARDs. To help address some of the knowledge gaps around the influence of b/tsDMARDs on COVID-19 outcomes, Sparks, et al. ana...

Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study

Wells AF, et al. Rheumatol Ther. 2021. Epub ahead of print. DOI: 10.1007/s40744-021-00317-9.

Wells AF,

Jia B,

Xie L,

Valenzuela GJ,

Keystone EC,

Li Z,

Quebe AK,

Griffing K,

Otawa S,

Haraoui B.

Analysis by Wells, et al. demonstrates long-term efficacy and tolerability of baricitinib 2 mg daily for up to 120 weeks in patients with rheumatoid arthritis.Using data from two completed phase III studies, RA-BEAM (csDMARD-IR patients) and RA-BEACON (TNFi-IR patients), and one ongoing long-term extension study (RA-BEYOND), results demonstrated that the long-term maintenance of clinically relevant treatment goals, including LDA, remission and normative physical function, is achievable with bari...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• LTE,
• Phase 3

Comparative efficacy and safety of secukinumab, ixekizumab, and tofacitinib in patients with active psoriatic arthritis showing insufficient response to tumor necrosis factor inhibitors

Int J Clin Pharmacol Ther. 2021. Epub ahead of print.

Song GG,

Lee YH.

Bayesian network meta-analysis of randomised controlled trials (RCTs) highlights the effectiveness of secukinumab, ixekizumab, and tofacitinib in patients with psoriatic arthritis (PsA) and an inadequate response to tumour necrosis factor inhibitors (TNFi).There is a current need for therapies with alternative mechanisms of actions to DMARDs and TNFi, for the significant proportion of patients with PsA who insufficiently respond to these therapies. While RCTs for therapies such as secukinumab a...

Keywords:

• JAK,
• IL-17,
• Secukinumab,
• Tofacitinib,
• Efficacy,
• Safety