March 2018

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis

Rheumatol Ther 2018 Jun; 5(1):203–14. DOI: 10.1007/s40744-018-0093-7

Methotrexate (MTX) or Glucocorticoid (GC) discontinuation has little effect on CDAI response in patients given tofacitinib (TOF) for up to 3 years. Patients receiving TOF who showed initial improvements benefitted from initiation of MTX or GCs. Concomitant treatments such as MTX or GC are commonly used in combination with RA therapies to improve or accelerate clinical responses. However, their use is associated with many adverse events so clinicians aim to use them for a minimal duration.This po...

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February 2018

Tofacitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Chinese Patients with Rheumatoid Arthritis: Patient-reported Outcomes from a Phase 3 Randomised Controlled Trial

Int J Rheum Dis 2018; 21(2):402–14

This Chinese sub-population of patients with RA from ORAL Sync reported significant improvements in patient-reported outcomes (PROs), which were maintained up to 12 months from tofacitinib (TOF) treatment initiation. ORAL Sync was a randomised, Phase 3 study investigating TOF therapy in combination with csDMARDs in patients with active RA who had previously had an inadequate response to csDMARDs. To date, this is the only Phase 3 study of TOF in patients from China with RA. This analysis include...

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November 2017

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

Arthritis Rheumatol 2017;69(10):1960–68

The results of this analysis of patients with herpes zoster (HZ) within the global tofacitinib (TOF) RA programme suggest that there is likely to be a greater HZ risk in patients receiving TOF and glucocorticoids compared with patients receiving TOF monotherapy.The global TOF RA development programme comprised 2 Phase 1, 9 Phase 2, 6 Phase 3 and 2 long-term extension studies. These studies included 6192 patients; data were reviewed to identify cases of HZ. Crude incidence rates of number of pati...

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August 2017

Treatment Persistence and Clinical Outcomes of Tumor Necrosis Factor Inhibitor Cycling or Switching to a New Mechanism of Action Therapy: Real-world Observational Study of Rheumatoid Arthritis Patients in the United States with Prior Tumor Necrosis Factor Inhibitor Therapy

Adv Ther. 2017 Aug;34(8):1936-1952. doi: 10.1007/s12325-017-0578-8

This retrospective, observational study used a real-world US clinical database to demonstrate greater effectiveness of switching to a therapy with an alternative mechanism of action (MOA) vs cycling between TNF inhibitors (TNFis) in patients in which TNFi therapy has failed.Between 1 April 2010 and 31 March 2015, a total of 613 of the observed patients failed a TNFi therapy and then either cycled to another TNFi therapy (54.2%) or switched to a therapy with an alternative MOA (45.8%). The most c...

July 2017

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

Ann Rheum Dis 2017;76:1253-1262. DOI 10.1136/annrheumdis-2016-210457

This analysis of exposure to tofacitinib, an oral JAKi for the treatment of RA, for up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. Adverse events were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.Data were collated into an integrated safety summary of tofacitinib in adult patients with active RA, and included data spanning the tofacitinib clinical programme: from 2 Pha...

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March 2017

A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti–Tumor Necrosis Factor Therapy

Arthritis Rheumatol 2016;68:2867–77

The summary and accompanying slide deck have been developed in conjunction with the Genovese et al. study (Study 1) which examined ABT-494 in MTX-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor.Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intolerant of...

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Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Arthritis Rheumatol 2016;68:2857–66

The summary and accompanying slide deck have been developed in conjunction with the Kremer et al. study (Study 2) which examined ABT-494 in TNF-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor.Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intolerant of p...

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February 2017

Analysis of Haematological Changes in Tofacitinib-treated Patients with Rheumatoid Arthritis across Phase 3 and Long-term Extension Studies

Rheumatology 2017;56:46–57.

In this analysis examining haematological changes after tofacitinib (TOF) treatment in patients with RA from pooled Phase 3 and LTE studies, TOF decreased mean lymphocyte counts and slightly increased mean haemoglobin (Hb) levels. The Phase 3 population included patients from six trials (n=4271) of TOF 5- or 10 mg BID, placebo or active comparator up to 24 months. The LTE population (n=4858) included patients from two studies (of up to 84 months), who had participated in Phase 1, 2 or 3 TOF stud...

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August 2016

A Randomized Phase 2b Study of ABT-494, a Selective JAK Inhibitor in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Arthritis Rheumatol 2016; Accepted article DOI 10.1002/art-39808 [Epub 2016]

This dose-ranging study evaluated the efficacy of the novel, selective JAK1 inhibitor ABT-494 versus placebo in patients with moderate-to-severe RA and inadequate response (IR) to MTX.In this 12-week, randomised, double-blind study (BALANCE II), the efficacy and safety ofABT-494 dosed at 3mg, 6 mg, 12 mg, 18 mg (all twice daily) and 24 mg (once daily) was assessed. Patients included had not received prior biologic therapy.Of the 299 patients included in the analysis, the proportions of patients ...

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May 2015

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

Ann Rheum Dis. 2015 Apr 22. pii: annrheumdis-2014-205847. doi: 10.1136/annrheumdis-2014-205847. [Epub ahead of print]

The developments of certain malignancies associated with chronic inflammatory diseases such as RA is known to occur to a greater extent than that of the general population. It is also know that certain RA treatments can affect malignancy rates. As such, newer immunomodulatory agents, such as the JAK inhibitor tofacitinib, are closely monitored for safety events of special interest, including malignancies.

This paper analyses pooled malignancy data from the tofacitinib RA clinical develop...

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