November 2019

Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase 2 and 3 Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis

Clin Pharmacol Ther . 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671.

UPA 15 mg provided the optimal benefit-risk in RA through maximizing efficacy with only small incremental benefit with 30 mg, and with consistency across RA subpopulations and with UPA monotherapy or combination with csDMARDs. Exposure-response analyses were conducted using combined data from two Phase 2b and five Phase 3 studies in order to characterise the relationship between plasma exposure and efficacy, as well as to select safety parameters using the totality of the data in subjects with R...

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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...

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September 2019

Comparison of Baricitinib, Upadacitinib, and Tofacitinib Mediated Regulation of Cytokine Signalling in Human Leukocyte Subpopulations

Arthritis Res Ther. 2019 Aug 2;21(1):183

Different JAKinibs modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signalling pathway throughout the dosing interval. This study aimed to compare the in vitro cellular pharmacology of BARI, TOF and UPA across relevant leukocyte subpopulations, coupled with their in vivo PK, to determine their effects on distinct cytokine pathways. Peripheral blood mononuclear cells from healthy donors were incubated with different JA...

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August 2019

Efficacy and Safety of Peficitinib (ASP015K) in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III Randomised, Double-Blind, Placebo-Controlled Trial (RAJ4) in Japan

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215164

Peficitinib (PEF) 100 and 150 mg demonstrated robust clinical and structural efficacy in patients with RA who have an inadequate response to MTX. In Japan, two JAK inhibitors, TOF and BARI are currently available for RA patients with an inadequate response to conventional therapies. This randomized phase 3 study (RAJ4), assessed the efficacy and safety of two PEF doses in combination with MTX compared to PBO, in Japanese MTX-IR. Patients were randomized 1:1:1 to PBO, PEF 100 mg and 150 mg with M...

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Effect of Filgotinib vs Placebo on Clinical Response in Patients with Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial

JAMA 2019 322(4):315-325

Among RA patients with an inadequate response or intolerance to bDMARDs, filgotinib (FIL) doses, compared to PBO resulted in significantly greater proportions achieving a clinical response at Wk12.Patients with active RA despite treatment with bDMARD therapy need treatment options. The FINCH 2 Phase 3 study compared the effects of FIL vs PBO for the treatment of RA patients with inadequate response or intolerance to ≥1 prior bDMARDs. Patients were randomized in a 1:1:1 ratio, receiving FIL 200 m...

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Safety and Effectiveness of Upadacitinib or Adalimumab Plus Methotrexate in Patients with Rheumatoid Arthritis Over 48 Weeks with Switch to Alternate Therapy in Patients with Insufficient Response

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215764

Consistent with Wk26 data, significantly more UPA patients achieved LDA and remission versus ADA and PBO over 48 weeks. RA patients often change therapy due to inadequate response and intolerance. The SELECT COMPARE study was designed to explore switching to JAK inhibitors from TNF inhibitors without a wash-out period (and vice versa). The long-term safety and efficacy of UPA was compared to ADA and PBO in MTX-IR.1629 patients were blindly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W and PBO, wi...

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Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): A randomised, double-blind, active-comparator-controlled Phase 3 trial

Lancet 2019;394:576–86. doi: 10.1016/S0140-6736(19)30952-3

Treatment with risankizumab showed significantly greater efficacy over adalimumab in providing substantial skin clearance in patients with moderate-to-severe chronic plaque PsO. This study aimed to assess the safety and efficacy of risankizumab compared with adalimumab in an active-comparator Phase 3 trial.

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July 2019

Live Zoster Vaccine in Patients with Rheumatoid Arthritis Treated with Tofacitinib with or without Methotrexate, or Adalimumab with Methotrexate

Arthritis Care and Research 2019 DOI: 10.1002/acr.24010

Live zoster vaccine (LZV) was well tolerated, and herpes zoster (HZ) incidence rates were generally similar between treatment groups in vaccinated versus non-vaccinated patients in a subset of RA who received LZV before TOF ± MTX, or ADA + MTX, in ORAL Strategy. It is known that patient with RA are at increased risk of developing HZ though the mechanisms behind this are currently not well understood though therapies, such as TOF, are thought to increase the risk. ACR and EULAR recommend using LZ...

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Clinical Outcomes in Patients Switched from Adalimumab to Baricitinib Due to Non-Response and/or Study Design: Phase III Data in Patients with Rheumatoid Arthritis

Ann Rheum Dis. 2019 Jul;78(7):890-898.

Switching from ADA to BARI without a lengthy washout period can be executed with acceptable safety and tolerability and was associated with maintained disease control. Switching therapies in RA is commonplace in myriad scenarios including inadequate responses, intolerances and patient preference. Assessing the safety and efficacy of new treatments such as BARI, in the context of use as a replacement therapy, is beneficial. A previous study (RA-BEACON) has demonstrated that safely switching from ...

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June 2019

Efficacy and Safety of Filgotinib for Patients With Rheumatoid Arthritis Naïve to Methotrexate Therapy: FINCH 3 Primary Outcome Results

EULAR 2019 Abstract LB0003 Presentation

Filgotinib is an orally administered, selective inhibitor of JAK1. Filgotinib has shown good efficacy and was well tolerated for the treatment of RA in Phase 2 and 3 studies evaluating MTX-IR or bDMARD-IR patients. The objective of this study was to compare the efficacy and safety of filgotinib with and without MTX in patients with RA who were naïve to MTX therapy....

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