May 2020

An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis Across Phase III and Long Term Extension Studies with Comparison to Real World Observational Data

Drug Saf. 2020;43:379-392

Patients with psoriatic arthritis (PsA) had similar safety profile with TOF to that of other systemic therapies in real-world settings, except for the known risk of HZ. Treatment recommendations from EULAR and GRAPPA for patients with PsA vary according to adverse prognostic risk factors, disease manifestations and responsiveness to prior treatment. Safety concerns for most PsA therapies include gastrointestinal AEs, hepatotoxicity, opportunistic infections (OIs) including TB, and SIEs. This stu...

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April 2020

Efficacy and safety of continuous risankizumab therapy vs treatment withdrawal in patients with moderate to severe plaque psoriasis: A Phase 3 randomized clinical trial

JAMA Dermatol 2020;156:649–58. doi 10.1001/jamadermatol.2020.0723

Blauvelt et al. shows superior and sustained efficacy for risankizumab in maintaining skin clearance over time versus placebo upon withdrawal, alongside a favourable safety profile in chronic plaque psoriasis through a phase 3, randomised, double-blind, placebo-controlled study, assessing PASI 90 and sPGA score of 0/1 at Week 16.

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December 2019

Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study

Rheumatol Ther . 2019 Dec;6(4):503-520. doi: 10.1007/s40744-019-00167-6. Epub 2019 Aug 13.

Peficitinib (PEF) 100 mg QD demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA in a two-year extension of two global phase IIb studies. Patients enrolled in the LTE had completed one of two 12-week phase IIb PEF trials, one with MTX and one without. The primary objective of the LTE was to assess treatment-emergent adverse events and clinical laboratory evaluations for 105 weeks. As a secondary objective, an additional 2-years of effectiveness ...

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Safety of Baricitinib in East Asian Patients With Moderate to Severe Active Rheumatoid Arthritis: An Integrated Analysis From Clinical Trials

Int J Rheum Dis . 2020 Jan;23(1):65-73. doi: 10.1111/1756-185X.13748.

Post-hoc analyses of five completed phase II and III trials and an ongoing LTE suggested that BARI QD is well tolerated in East Asian patients with moderate-to-severe RA, with a similar safety and tolerability profile to the overall population.The majority of clinical evidence for RA treatments has been obtained from a predominantly Caucasian population, which may not be relevant to East Asian patients. In this post-hoc safety analysis, 740 Japanese, Taiwanese, Korean and Chinese patients were i...

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November 2019

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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A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis

Rheumatology (Oxford) 2019;58(10):1755–66

Absolute serious infection rates were low. However, across the JAKinibs, the incidence of HZ is higher than expected for the population. While the risk was numerically greatest with BARI, indirect comparisons between the drugs did not demonstrate any significant difference in risk. How JAKinibs increase the risk of HZ reactivation is unclear, but how different JAKs interact in the immune response suggest that there may be differences in safety profiles between JAKinib drugs, underpinned by their...

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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

Upadacitinib versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase 3, Double-Blind, Randomized Controlled Trial

Arthritis Rheumatol 2019 DOI: 10.1002/art.41032

UPA demonstrated superiority to ADA in terms of clinical, functional and patient-reported outcomes with comparable radiographic inhibition. As many RA patients fail to achieve LDA and remission with TNF inhibitors and MTX there is a requirement for additional treatment options. In this SELECT-COMPARE study the clinical and functional outcomes of UPA were compared to ADA in MTX-IR patients. 1629 MTX-IR were randomly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W or PBO, with background MTX. Key end...

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May 2019

A Systematic Review and Meta-Analysis of Infection Risk with Small Molecule JAK Inhibitors in Rheumatoid Arthritis

Rheumatology (Oxford). DOI: 10.1093/rheumatology/kez087

How JAKinibs increase the risk of HZ reactivation is unclear. Roles of different JAKs in the immune response may suggest differences in safety profiles between drugs, underpinned by their differential JAK selectivity profiles. The authors undertook a systematic review and meta-analysis to evaluate SI and opportunistic indicator infections including HZ in RA Phase II/III clinic trials with JAKinibs. A literature review of RCT of TOF (5 mg BID), BARI (4 mg OD) and UPA (15 mg OD) was conducted. A p...

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Safety and Efficacy of Tofacitinib For Up to 9.5 Years in The Treatment of Rheumatoid Arthritis: Final Results of a Global, Open-Label, Long-Term Extension Study

Arthritis Res Ther. 2019 Apr 5;21(1):89.

TOF 5 mg and 10mg BID demonstrated a consistent safety profile and sustained efficacy for up to 9.5 years in this open-label LTE ORAL Sequel study.TOF 5 mg and 10 mg BID demonstrated consistent safety (as monotherapy and combination therapy) and efficacy within this open-label LTE study of RA patients. As RA requires long-term treatment, it’s important to assess the long-term efficacy and safety of RA therapies to understand the potential lifelong impact on patient health and quality of life. Th...

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