Publications
View and download slide summaries of the latest original articles focusing on cytokine signalling therapies within rheumatoid arthritis. All materials produced by the CSF team are subsequently reviewed and approved by individual steering committee members.
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
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...
Infections in Baricitinib Clinical Trials for Patients with Active Rheumatoid Arthritis
Annals of the Rheumatic Diseases, May 2020
Baricitinib, an oral selective JAK1 and JAK2 inhibitor,8 demonstrated significant clinical efficacy in phase 3 RA trials. Pooled data from these trials, including a long-term extension (LTE), inform the safety profile for baricitinib, mainly to evaluate the incidence of infection in patients with active rheumatoid arthritis (RA), with a focus on serious infection, tuberculosis (TB), herpes zoster (HZ) and opportunistic infection (OI). The data collected were from eight double-blind randomised tr...
Long-term Effectiveness of Live Herpes Zoster Vaccine in Patients with Rheumatoid Arthritis Subsequently Treated with Tofacitinib
Ann Rheum Dis. 2020 10.1136/annrheumdis-2019-216566
The results of ORAL Sequel suggest that the live zoster vaccine (LZV) may not provide adequate long-term protection in patients with RA receiving TOF. This LTE study enrolled 100 patients with RA, 14 weeks post LZV vaccination. Patients received either TOF 5 mg BID, or TOF 10 mg BID in addition to any background csDMARDs. Incidence rates and 95% CIs for HZ post-vaccination were calculated based on time to first event. Short-term varicella zoster vaccine (VZV) specific immunity was evaluated at ...
Comparative Efficacy and Safety of Peficitinib 25, 50, 100, and 150 mg in Patients with Active Rheumatoid Arthritis: A Bayesian Network Meta‑Analysis of Randomized Controlled Trials
Clin Drug Investig .2020 Jan;40(1):65-72. doi: 10.1007/s40261-019-00863-9.
PEF 50, 100, and 150 mg once daily was effective in treating active RA, without causing a significant risk for AEs.Intracellular pathways, including JAK and Tyk-2, are critical for immune cell activation, pro-inflammatory cytokine production, and cytokine signaling. PEF has been developed for use in RA, but the comparative efficacy and safety of regimens and dosages has not been established. A Bayesian network meta-analysis was conducted to combine direct and indirect evidence to assess the rela...
Tofacitinib Modulates the VZV-specific CD4+ T Cell Immune Response in vitro in Lymphocytes of Patients with Rheumatoid Arthritis
Rheumatology (Oxford) 2019;58(11):2051–60
TOF significantly modulated the Th1 response to Varicella-zoster-virus (VZV). The poor VZV-specific cellular immune responses in patients with RA may be considered in recommendations regarding appropriate vaccination strategies for enhancing the VZV-specific Th1 response.Previous studies have shown that treatment with JAKinibs increases HZ incidence compared with conventional DMARDs. This cross-sectional in vitro study aimed to investigate the effect of TOF on the VZV-specific T cell immune resp...
Evaluation of Pneumococcal and Tetanus Vaccine Responses in Patients with Rheumatoid Arthritis Receiving Baricitinib: Results from a Long-Term Extension Trial Substudy
Arthritis Res Ther. 2019 Apr 18;21(1):102
Approximately two thirds of long-term BARI treated patients achieved satisfactory humoral and functional responses to 13-serotype pneumococcal conjugate vaccine (PCV-13), whereas tetanus toxoid vaccine (TTV) responses were less robust. Both RA management guidelines and recommendations suggest vaccinating patients with RA against pneumococcal disease with PCV-13 and PPSV-23. The inhibition of the JAK mediated signal transduction pathways in RA treatment could diminish vaccine responses. Given the...
Herpes zoster in Tofacitinib: Risk is Further Increased with Glucocorticoids but not Methotrexate
Arthritis Care Res 2018 DOI 10.1002/acr.23769
The rate of Herpes Zoster (HZ) in tofacitinib (TOF) users with concomitant glucocorticoids (GC) was approximately double that of other TOF combination therapies.TOF is an effective treatment for RA. Increased HZ risk has been observed with the use of JAK inhibitors, whereas the HZ risk with biologics and targeted RA therapies are comparable. This study evaluated the HZ risk in TOF users according to concomitant GC, MTX, both, or neither. MarketScan and Medicare data were used to identify 8030 rh...
The Safety and Immunogenicity of Live Zoster Vaccination in Rheumatoid Arthritis Patients Before Starting Tofacitinib: A Randomized Phase II Trial
Arthritis Rheumatol. 2017 Oct;69(10):1969-1977. doi: 10.1002/art.40187
Patients with RA who started treatment with tofacitinib 2–3 weeks after being vaccinated against herpes zoster had similar varicella zoster virus (VZV)-specific humoral and cell-mediated responses to the live vaccine compared to patients who received placebo.In this Phase 2 study, humoral and cell-mediated immune responses were evaluated before receipt of live zoster vaccine (LZV) and at 2, 6 and 14 weeks after vaccination, having been randomised to tofacitinib 5 mg BID or placebo, 2–3 weeks aft...
The Emerging Safety Profile of JAK Inhibitors in Rheumatic Disease
Nature Reviews Rheumatology 2017;13:234–43
This review discusses the current understanding of the safety of JAK inhibitors, including providing an overview of the changes in laboratory parameters, infection and malignancy risks associated with each JAK inhibitor compound.The review discusses the adverse event profiles and cellular changes characteristically seen with each JAK inhibitor, as well as the overlap or differences between the various compounds. The relative specificities for different JAKs between each compound do not always p...
Real-world Comparative Risks of Herpes Virus Infections in Tofacitinib and Biologic-treated Patients with Rheumatoid Arthritis
Ann Rheum Dis. 2016 Apr 25;0:1–5 doi: 10.1136/annrheumdis-2016-209131
Herpes Zoster (HZ) complications can cause considerable morbidity including debilitating pain syndromes. Clinical trials of tofacitinib have suggested it may increase the risk of HZ. Although unclear, the mechanism may involve reduced CD4 T-cell function and interference of interferon signalling. Following approval of tofacitinib in the US in 2012, real-world data from Medicare (2006–2013) and from the US longitudinal database, Marketscan, (2010–2014) were analysed. A total of 2526 patients who...