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

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Rheumatol Ther. 2022 doi: 10.1007/s40744-021-00410-z

Burmester G,

Winthrop K,

Blanco R,

Nash P,

Goupille P,

Azevedo V,

Salvarani C,

Rubbert-Roth A,

Lesser E,

Lippe R,

Lertratanakul A,

Mccaskill RM,

Liu J,

Ruderman EM

Upadacitinib 15 mg once daily demonstrated a similar safety profile to adalimumab 40 mg every other week, except for higher rates of HZ and opportunistic infections with upadacitinib treatment in patients treated for PsA

Keywords:

• JAK,
• Updacitinib,
• Phase 3,
• Safety

Immune‑related adverse events (irAEs) in ankylosing spondylitis (AS) patients treated with interleukin (IL)‑17 inhibitors: a systematic review and meta‑analysis

Inflammopharmacology. 2022, Apr;30(2):435-451. doi: 10.1007/s10787-022-00933-z

Azadeh H,

Alizadeh-Navaei R,

Rezaiemanesh A,

Rajabinejad M

The most common immune system-related AEs in patients treated with IL-17 inhibitors are mucosal and opportunistic infections.

Interleukin (IL)-17 inhibitors are a series of biological drugs used to treat a number of conditions, including ankylosing spondylitis, a disease characterised by immune system dysregulation and joint inflammation. Azadeh, et al. aimed to assess the risk of immune system-related AEs due to targeting IL-17 or IL-17R.

Keywords:

• IL-17,
• Meta analysis,
• Safety,
• Review

Oral surveillance and JAK inhibitor safety: the theory of relativity

Nat Rev Rheumatol. 2022. Epub ahead of print doi: 10.1038/s41584-022-00767-7

Winthrop KL,

Cohen SB.

Putting the data into context, Winthrop, et al. conclude that the ORAL Surveillance data are not dissimilar to those from the original developmental programme, which suggested additional safety concerns at the 10 mg dosage and that resulted in the 5 mg twice daily dosage as the approved dose for RA.Following the recent results of the ORAL Surveillance (ORALSURV) study, and the consequent changes to the utilisation of JAKinibs, made by the regulatory authorities, Winthrop, et al. aim to put the O...

Keywords:

• JAK,
• Tofacitinib,
• Safety

Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study

RMD Open. 2022;8(1):e002012 doi: 10.1136/rmdopen-2021-002012

Fleischmann R,

Mysler E,

Bessette L,

Peterfy CG,

Durez P,

Tanaka Y,

Swierkot J,

Khan N,

Bu X,

Li Y,

Song IH

Upadacitinib continues to show consistently better clinical responses, compared with adalimumab, through 3 years, including rates of remission and low disease activity, physical function and pain severity.Following the favourable upadacitinib efficacy data seen in the SELECT-COMPARE study at 72 weeks, Fleischmann, et al. assessed the long-term safety and efficacy of upadacitinib versus adalimumab over 3 years in the long-term extension of this study, with promising results. ...

Keywords:

• JAK,
• Updacitinib,
• Safety,
• Efficacy,
• LTE

Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)

Clin Rheumatol. 2022 Jan 1. Epub ahead of print doi: 10.1007/s10067-021-05908-z

Mueller RB,

Schulze-Koops H,

Furst DE,

Cohen SB,

Kwok K,

Wang L,

Killeen T,

von Kempis J

Post-hoc analysis shows that dosing up from tofacitinib 5 to 10 mg BID is associated with improved efficacy for up to 12 months, versus staying on 5 mg BID, and dosing down from 10 to 5 mg BID is not generally associated with a significant loss of efficacy.Although clinical trials have generally shown no significant differences, in terms of efficacy and safety, when switching tofacitinib dose up or down, these per-protocol switches are not directly informative for clinical decision-making in dai...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Efficacy,
• Dosing

Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis

Clin Rheumatol. 2022. Epub ahead of print doi: 10.1007/s10067-021-06003-z

Li N,

Gou ZP,

Du SQ,

Zhu XH,

Lin H,

Liang XF,

Wang YS,

Feng P.

Systematic review and network meta-analysis highlight that RA patients who receive recommended doses of the five approved JAK inhibitors (tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib) are likely to experience an increase in serum low- and high-density lipoprotein (LDL and HDL) levels.JAK inhibitors have been associated with alterations in levels of LDL and HDL cholesterol, which may lead to dyslipidaemia (an important risk factor for cardiovascular disease). However, the e...

Keywords:

• JAK,
• Meta analysis,
• Review

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

Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment

Rheumatol Ther. 2021. Epub ahead of print. doi: 10.1007/s40744-021-00390-0

Winthrop KL,

Curtis JR,

Yamaoka K,

Lee EB,

Hirose T,

Rivas JL,

Kwok K,

Burmester GR

This post hoc analysis provides the first detailed description of the management and outcomes of HZ events in tofacitinib RA and PsA clinical studies.While prior studies have characterised the increased HZ risk with JAKinibs, the clinical management of these events has not been detailed.To this end, Winthrop, et al. analysed data from 21 RA and 3 PsA clinical studies to evaluate how HZ events and their sequelae were clinically managed during the RA and PsA tofacitinib clinical development progra...

Keywords:

• JAK,
• Tildrakizumab,
• Safety,
• Infections