Publications

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

Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years

Ann Rheum Dis. 2021. Epub ahead of print. doi: 10.1136/annrheumdis-2021-221051

Winthrop KL,

Tanaka Y,

Takeuchi T,

Kivitz A,

Matzkies F,

Genovese MC,

Jiang D,

Chen K,

Bartok B,

Jahreis A,

Besuyen R,

Burmester GR,

Gottenberg JE

Integrated analysis evaluates the safety of filgotinib among patients with RA treated for a median of 1.6 years.Winthrop, et al. analysed data from seven trials, including long-term extension studies, and found that rates of TEAEs, grade ≥3 TEAEs, serious TEAEs and TEAEs leading to study drug discontinuation were comparable for filgotinib and placebo. In addition, analysis of AEs of special interest showed a generally similar incidence for filgotinib 200 mg and 100 mg....

Keywords:

• JAK,
• Fenebrutinib,
• Safety,
• Review

Filgotinib Versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and Inadequate Response to Methotrexate: A Phase III Randomised Clinical Trial

Ann Rheum Dis. 2021 Jan 27:annrheumdis-2020-219214

Combe B,

Kivitz A,

Tanaka Y,

van der Heijde D,

Simon JA,

Baraf HSB,

Kumar U,

Matzkies F,

Bartok B,

Ye L,

Guo Y,

Tasset C,

Sundy JS,

Jahreis A,

Genovese MC,

Mozaffarian M,

Landewé RBM,

Bae S-C,

Keystone EC,

Nash P

Filgotinib improved RA signs and symptoms, physical function, and inhibited radiographic progression. FIL 200mg plus MTX, but not FIL 100mg plus MTX showed non-inferiority to ADA plus MTX, based on DAS28(CRP) low disease activity. FIL was also well tolerated in RA patients with inadequate response to MTX.This 52-week, phase 3 randomised clinical trial (FINCH 1) evaluated the efficacy and safety of FIL in patients with RA randomised to FIL 200 or 100mg, ADA 40mg, or placebo, all with background M...

Keywords:

• JAK,
• Fenebrutinib,
• Phase 3

Safety and Efficacy of Tofacitinib in Patients with Active Psoriatic Arthritis: Interim Analysis of OPAL Balance, an Open-Label, Long-Term Extension Study

Rheumatol Ther 2020 doi.org/10.1007/s40744-020-00209-4

Nash P,

Coates LC,

Kivitz AJ,

Mease PJ,

Gladman DD,

Covarrubias-Cobos JA,

FitzGerald O,

Fleishaker D,

Wang C,

Wu J,

Hsu M,

Menon S,

Fallon L,

Romero AB,

Kanik KS

This 3-year, open-label, LTE study follows PsA patients previously treated in pivotal studies OPAL Broaden and OPAL Beyond. It demonstrates maintained safety and efficacy of tofacitinib up to 36 and 30 months, respectively. No new safety concerns are highlighted. Previous P3 studies, OPAL Broaden and OPAL Beyond, demonstrated safety and efficacy of 5mg and 10mg tofacitinib BID in PsA. These patients rolled over to OPAL Balance for a period of 36 months. 686 participants were used in this interim...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Efficacy,
• LTE

A Pooled analysis of the Safety of Tofacitinib as Monotherapy or in Combination with Background Conventional Synthetic Disease-Modifying Antirheumatic Drugs in a Phase 3 Rheumatoid Arthritis Population

Semin Arthritis Rheum. 2018 Dec;48(3):406-415. doi: 10.1016/j.semarthrit.2018.07.006.

Kivitz AJ,

Cohen S,

Keystone E,

van Vollenhoven RF,

Haraoui B,

Kaine J,

Fan H,

Connell CA,

Bananis E,

Takiya L,

Fleischmann R

In this pooled analysis of Phase 3 Tofacitinib (TOF) trials, safety profiles were generally similar between patients receiving monotherapy and combination therapy. Although selected adverse events of interest showed lower incidence rates (IRs) for TOF monotherapy patients.TOF has been studied as monotherapy and in combination with csDMARDs. In this post-hoc analysis, data were pooled from six Phase 3 TOF studies in RA patients to further examine the safety profile when used as monotherapy or in ...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• Meta analysis

Professor Iain McInnes Reviews the Most Notable Papers from 2018

Please click the links below to go to the CSF review of each paper

McInnes. I

2018 brought a wealth of new data in cytokine signalling and IL-6 that helps inform current clinical practice and brings the promise of new options in the future. There was good data on the use of sub cutaneous tocilizumab as well as strategies in early RA and for methotrexate tapering. For the currently marketed JAK inhibitors, tofacitinib and baricitinib, continuous long-term efficacy and safety data further support its current use and applications. On the development side, the outcomes of the...

Keywords:

• Review

Safety and Efficacy of Upadacitinib in Patients with Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (SELECT-NEXT): a Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial

Lancet 2018;391:2503–12

Burmester GR,

Kremer JM,

Van den Bosch F,

Kivitz A,

Bessette L,

Li Y,

Zhou Y,

Othman AA,

Pangan AL,

Camp HS

Patients with moderate-to-severe active RA had significant improvements in clinical signs and symptoms with upadacitinib (UPA) compared with placebo.In Phase 2 studies, UPA showed favourable efficacy when administered twice daily as an immediate-release formulation at doses of 6–12 mg in patients with active RA who had TNFi-IR.1,2 An extended-release formulation allowing once-daily (QD) administration was developed for Phase 3 studies. SELECT-NEXT was a double-blind, multicentre, Phase 3 study t...

Keywords:

• JAK,
• Updacitinib,
• Phase 3

Long-term Radiographic and Patient-reported Outcomes in Patients with Rheumatoid Arthritis Treated with Tofacitinib: ORAL Start and ORAL Scan Post-hoc Analyses

Rheumatol Ther. 2018 Dec;5(2):341-353. doi: 10.1007/s40744-018-0113-7

Strand V,

Kavanaugh A,

Kivitz AJ,

van der Heijde D,

Kwok K,

Akylbekova E,

Soonasra A,

Snyder M,

Connell C,

Bananis E,

Smolen JS

Tofacitinib (TOF) therapy reduced the progression of structural joint damage at 2 years, in patients of all disease states, compared with patients given methotrexate (MTX). Early intervention with DMARDs aim to prevent the development of future RA symptoms and inhibit the progression of structural damage to the joints. This post-hoc analysis uses data from two Phase 3 TOF studies, to examine the efficacy of early intervention with TOF on long-term radiographic outcomes and disease activity state...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• PRO / QoL,
• Radiographic

Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis

J Rheumatol 2018 Apr; 45(4):456-464

Kivitz A,

Olech E,

Borofsky MA,

Zazueta B,

Navarro-Sarabia F,

Radominski SC,

Merrill JT,

Pacheco-Tena C,

Pei J,

Nasmyth-Miller,

Pope JE

This 2-year Phase 3 study, proved that subcutaneous tocilizumab (TC-SC) has long-term efficacy and an acceptable safety profile. Patients enrolled had been previously diagnosed with RA with an inadequate response to DMARDs. Patients were randomised 2:1 to receive doses of TCZ-SC (n=437) or PBO (n=219) every other week for 6 months. After this time, all patients received TCZ-SC. Escape therapy, defined as weekly TCZ-SC, was available to patients from Month 3. Efficacy was analysed using ACR respo...

Efficacy and Safety of Tofacitinib Monotherapy, Tofacitinib with Methotrexate, and Adalimumab with Methotrexate in Patients with Rheumatoid Arthritis (ORAL Strategy): A Phase 3b/4, Double-Blind, Head-To-Head, Randomised Controlled Trial

Lancet. 2017 Jul 29;390(10093):457-468. doi: 10.1016/S0140-6736(17)31618-5

Fleischmann R,

Mysler E,

Hall S,

Kivitz A,

Moots R,

Luo Z,

DeMasi R,

Soma K,

Zhang R,

Takiya L,

Tatulych S,

Mojcik C,

Krishnaswami S,

Menon S,

Smolen J,

on behalf of the ORAL Strategy investigators

In this first head-to-head non-inferiority trial assessing a JAKi ± MTX directly compared with a TNFi + MTX in patients with RA, tofacitinib (TOF) + MTX showed non-inferiority to adalimumab (ADA) + MTX. Non-inferiority was not shown for TOF monotherapy versus TOF + MTX, or versus ADA + MTX.In this 52-week study, MTX-inadequate responder (IR) patients were randomised 1:1:1 to receive TOF 5 mg BID monotherapy, TOF 5 mg BID + MTX or ADA 40 mg every other week + MTX. The primary endpoint, ACR50 resp...

Keywords:

• JAK,
• Tofacitinib,
• Phase 4,
• Phase 3