Publications

Is the Risk of Infection Higher During Treatment with Secukinumab than with TNF-inhibitors? An Observational Study from the Nordic Countries

Rheumatology (Oxford). 2022 doi: 10.1093/rheumatology/keac358

Glintborg B,

Giuseppe DD,

Wallman JK,

Provan SA,

Nordström D,

Hokkanen AM,

Österlund J,

Kristianslund E,

Kvien T,

Gudbjornsson B,

Hetland ML,

Michelsen B,

Jacobsson L,

Askling J,

Lindström U.

Glintborg B et al, highlight in their recent research from the Nordic countries, that there is a low frequency of hospitalised infections during treatment with secukinumab or TNFi in patients with SpA and PsA. In clinical practice, secukinumab was found to double absolute risk of 1st year hospitalised infection compared with adalimumab, with the other TNFi treatments falling in between.

Keywords:

• IL-17,
• Secukinumab,
• Safety,
• Infections

Identification of novel off targets of baricitinib and tofacitinib by machine learning with a focus on thrombosis and viral infection

Sci Rep. 2022 doi: 10.1038/s41598-022-11879-1

Faquetti ML,

Grisoni F,

Schneider P,

Schneider G,

Burden AM

Established machine learning approaches, based on ligand similarity, identified previously unknown off-target interactions of baricitinib and tofacitinib, and adds to the evidence that these JAK inhibitors are promiscuous binders, and highlight the potential for repurposing.

Keywords:

• JAK,
• Baricitinib,
• Tofacitinib,
• Safety,
• Infections,
• Thrombosis

Unincreased risk of hospitalized infection under targeted therapies versus methotrexate in elderly patients with rheumatoid arthritis: a retrospective cohort study

Arthritis Res Ther. 2022 doi: 10.1186/s13075-022-02807-9

Sakai R,

Tanaka E,

Majima M,

Harigai M

Retrospective, longitudinal, population-based study shows that despite an overall higher incidence of hospitalised infection (HI) in both elderly and older elderly patients compared to young patients, the risks of HI in patients exposed to targeted therapy versus MTX is not significantly increased.

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

Evaluation of response to 13-valent conjugated pneumococcal vaccination in patients with rheumatoid arthritis receiving upadacitinib: results from a phase 2 open-label extension study

RMD Open. 2022;8(1):e002110 doi: 10.1136/rmdopen-2021-002110

Winthrop K,

Vargas JI,

Drescher E,

Garcia C,

Friedman A,

Hendrickson B,

Li Y,

Klaff J,

Kivitz A

Vaccine sub-study of the BALANCE-EXTEND upadacitinib trial finds that approximately two-thirds of patients receiving upadacitinib 15 mg once-daily achieve a satisfactory humoral response to pneumococcal 13-valent conjugate (PCV-13) vaccine, despite receiving concomitant methotrexate (MTX).It is well known that a weakened immune response, comorbidities and immunosuppressant drug therapy all contribute to an increased susceptibility to infections in patients with RA. Likewise, the morbidity and mo...

Keywords:

• JAK,
• Updacitinib,
• Vaccination

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

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

Ann Rheum Dis. 2021. Epub ahead of print. doi: 10.1136/annrheumdis-2021-220822.

Winthrop KL,

Nash P,

Yamaoka K,

Mysler E,

Khan N,

Camp HS,

Song Y,

Suboticki JL,

Curtis JR

JAKinibs have been linked with an increased risk of HZ in patients with RA. To this end, Winthrop, et al. evaluated data from six Phase III clinical trials to determine the incidence of HZ in the upadacitinib (UPA)-treated patients with RA and identify potential risk factors for the development of HZ in these patients.Analysis of data provides further support for the need for continued vigilance and monitoring for signs of herpes zoster (HZ) in patients receiving UPA, particularly in Asian popul...

Keywords:

• JAK,
• Updacitinib,
• Phase 3,
• Safety,
• Meta analysis,
• Infections

Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib

Int J Rheum Dis. 2021. Epub ahead of print

Wang ST,

Tseng CW,

Hsu CW,

Tung CH,

Huang KY,

Lu MC,

Lai NS.

Tofacitinib could induce Hepatitis B virus (HBV) reactivation in RA patients.With previous studies having already demonstrated that RA patients using biologic agents, might experience HBV reactivation leading to acute hepatitis, hyperbilirubinemia, and death, Wang, et al. aimed to investigate HBV reactivation in patients with RA receiving tofacitinib. They found that Hepatitis B surface antigen positive patients receiving tofacitinib have a high incidence rate of HBV reactivation, which could be...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections

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