Publications

Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis

N Engl J Med. 2024;391:1119-1129 doi: 10.1056/NEJMoa23140

Sands BE,

Feagan BG,

Peyrin-Biroulet L,

Danese S,

Rubin DT,

Laurent O,

Luo A,

Nguyen DD,

Lu J,

Yen M,

Leszczyszyn J,

Kempiński R,

McGovern DPB,

Ma C,

Ritter TE,

Targan S

Sands et al. demonstrated that 12-week treatment of tulisokibart, a monoclonal antibody targeting TL1A, significantly improved clinical remission rates compared to placebo in patients with moderate-to-severe ulcerative colitis.

Keywords:

• Remission

Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme

Ann Rheum Dis. 2023 doi: 10.1136/ard-2023-223916

Fleischmann R,

Curtis JR,

Charles-Schoeman C,

Mysler E,

Yamaoka K,

Richez C,

Palac H,

Dilley D,

Liu J,

Strengholt S,

Burmester G

Pots hoc analysis of safety data in patients with RA at increased risk of CV events from the upadacitinib SELECT phase III RA clinical programme helps to contextualise the overall risk profile of upadacitinib.

Keywords:

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

Impact of Cardiovascular Risk Enrichment on Incidence of Major Adverse Cardiovascular Events in the Tofacitinib Rheumatoid Arthritis Clinical Programme

Ann Rheum Dis. 2023;82(4):575–577 doi: 10.1136/ard-2022-223406

Dougados M,

Charles-Schoeman C,

Szekanecz Z,

Giles JT,

Ytterberg SR,

Bhatt DL,

Koch GG,

Vranic I,

Wu J,

Wang C,

Kwok K,

Menon S,

Connell CA,

Yndestad A,

Rivas JL,

Buch MH

Data suggest that an important difference between P123LTE and ORAL Surveillance was the proportion of patients with a history of atherosclerotic CV disease (ASCVD).

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Cardiovascular

Safety Profile of Upadacitinib in Rheumatoid Arthritis: Integrated Analysis from the SELECT Phase III Clinical Programme

Ann Rheum Dis 2020 DOI:10.1136/annrheumdis-2020-218510

Cohen SB,

van Vollenhoven RF,

Winthrop KL,

Zerbini CAF,

Tanaka Y,

Bessette L,

Zhang Y,

Khan N,

Hendrickson B,

Enejosa JV,

Burmester GR.

This integrated Phase III safety analysis of UPA showed that UPA had a similar profile to ADA and MTX for serious infections, malignancies, and thromboembolic events. Patients receiving UPA had increased risk of HZ and creatine phosphokinase elevation versus ADA.This integrated Phase III safety analysis of UPA examined >3500 RA patients and 4000 patient-years of exposure. Data were pooled from 3834 patients in SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY studie...

Keywords:

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

Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland

RMD Open 2020;6:e001174 doi:10.1136/rmdopen-2020-001174

Finckh A,

Tellenbach C,

Herzog L,

Scherer A,

Moeller B,

Ciurea A,

von Muehlenen I,

Gabay C,

Kyburz D,

Brulhart L,

Müller R,

Hasler P,

Zufferey P

This nested cohort study found that, in Switzerland, there was a generally limited overall drug maintenance for b/tsDMARD options in RA. Using data from SCQM-RA – a prospective longitudinal registry, overall maintenance (drug survival) was calculated for TNFi, bDMARD-OMA or JAKi in patients with RA.After adjusting for potential confounding factors, there was a higher hazard of drug discontinuation with TNFi compared with tofacitinib; no significant difference was observed between non-TNF bDMARDs...

Keywords:

• JAK,
• Tofacitinib,
• Real-World,
• Efficacy

Safety, Tolerability, Pharmacokinetics, Target Occupancy, and QT Analysis of the Novel BTK Inhibitor Evobrutinib in Healthy Volunteers

Clin Transl Sci . 2020 Mar;13(2):325-336. doi: 10.1111/cts.12713. Epub 2019 Nov 29.

Becker A,

Martin EC,

Mitchell DY,

Grennigloh R,

Bender AT,

Mackenzie H and Johne A

In this first in-human phase I, double-blind, placebo-controlled trial, the Bruton’s tyrosine kinase (BTK) inhibitor evobrutinib was well-tolerated, showed linear and time-independent PK, induced long-lasting BTK inhibition, and was not associated with prolongation of QT/QTc interval in healthy subjects. Evobrutinib is an oral BTK inhibitor that has demonstrated efficacy in pre-clinical and autoimmune disease models. BTK is a key regulator of B cell receptor and Fc receptor signalling, and a rat...

Keywords:

• BTK,
• Evobrutinib,
• Safety,
• MOA

Eventi Avversi, Considerazioni Cliniche e Raccomandazioni per la gestione dei Pazienti con Artrite Reumatoide Trattati con Inibitori di JAK

Exp Rev Clin Immunol 2018 Nov;14(11):945-956. DOI: 10.1080/1744666X.2018.1504678

Atzeni F,

Talotta R,

Nucera V,

Marino F,

Gerratana E,

Sangari D,

Masala IF,

Sarzi-Puttini P

Janus kinase (JAK) inhibitors are efficacious in patients with moderate-to-severe RA and have a favourable safety profile. However adverse events (AE), in particular infections, are associated with the use of JAK inhibitors. This paper reviews the mechanism behind JAK inhibitors, the AEs associated with them, and provides consideration in the management of AEs in clinical practice. Data on two RA approved JAK inhibitors – tofacitinib (TOF) and baricitinib (BARI) – was obtained using PubMed, Medl...

Keywords:

• JAK,
• Safety,
• Review

Farmacocinetica di Upadacitinib con Regimi Clinici della Formulazione a Rilascio Prolungato Utilizzata in Sperimentazioni di Fase 3 in Artrite Reumatoide

Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462

Mohamed MEF,

Zeng J,

Marroum PJ,

Song IH,

Othman AA

Upadacitinib (UPA) extended release (ER) formulation dosing achieved the target profile that enables single dosing in patients with RA. In early clinical studies, UPA was given as an immediate release (IR) formulation, however patients were noted to experience fluctuations in blood plasma concentrations. To enhance patient compliance in UPA Phase 3 trials, ER tablets have been developed. Here, authors aimed at characterising the pharmacokinetics of UPA single and multiple doses of ER compared wi...

Keywords:

• JAK,
• Updacitinib,
• PK/PD

Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program

Arthritis Care Res (Hoboken). 2018 May;70(5):685-694. doi: 10.1002/acr.23421

Mariette X,

Chen C,

Biswas P,

Kwok K,

Boy MG

Analysis of 19 studies involving the use of tofacitinib to treat RA showed that lymphoma incidence rate and type were consistent with expectations in the RA population as a whole, and did not increase with tofacitinib exposure time.Previous research has suggested that there is a link between the likelihood of developing malignant tumours and RA. Previously, it has been unclear whether the increased rates seen are due to the use of immunomodulatory therapies, such as tofacitinib, which are used a...

Keywords:

• JAK,
• Tofacitinib,
• Phase 2,
• Phase 3,
• Malignancy

Analysis of Non-melanoma Skin Cancer across the Tofacitinib Rheumatoid Arthritis Clinical Programme

Clin Exp Rheumatol 2017;35:614–22

Curtis JR,

Lee EB,

Martin G,

Mariette X,

Terry TT,

Chen Y,

Geier J,

Andrews J,

Kaur M,

Fan H,

Nduaka CI

Because non-melanoma skin cancer (NMSC) is one of the most common malignancies associated with RA immunomodulatory therapies, this analysis looked to determine the rate of NMSC incidence per 100 patient-years in patients with RA receiving TOF in the clinical trial programme. The Phase 1, 2, and 3 IRs (combined) for both TOF 5- and 10 mg were low and comparable to those of adalimumab, MTX and placebo, IRs remained stable over time. TOF doses used in the 2 Phase 1; 8 Phase 2; and 6 Phase 3 studies...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Skin,
• Malignancy