March 2021

Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program

Drug Saf. 2021 Feb 2. DOI: 10.1007/s40264-020-01036-w

Upadacitinib 15 mg has a favourable benefit–risk profile according to an assessment of data from the phase III SELECT clinical trial programme.In this review of data for the once-daily, oral JAK inhibitor, Conaghan PG, et al. provided insights into the benefit–risk profile of upadacitinib in approximately 4400 patients with RA. Based on pooled data from five pivotal studies, benefits and risks were assessed up to the time of regulatory submission, and additional long-term integrated safety revie...

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February 2021

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

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...

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November 2020

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

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...

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Age-Based (<65 vs ≥65 years) Incidence of Infections and Serious Infections with Tofacitinib Versus Biological DMARDs in Rheumatoid Arthritis Clinical Trials and the US Corrona RA Registry

Ann Rheum Dis 2020; DOI: 10.1136/annrheumdis-2020-218992

Reports from clinical trials and the US Corrona RA registry showed that serious infection event (SIE) incidence was higher in older versus younger patients with RA receiving 10 mg BID of TOF and ADA, however, SIE risk was similar between age groups with TOF 5 mg BID and ADA.Data were collected from Phase II–IV tofacitinib studies, and the US Corrona RA registry. The clinical data set evaluated patients receiving TOF 5 and 10 mg BID versus TNFi (ADA/ETN) in RA patients aged ≥50 years. The EMA rec...

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May 2020

Fenebrutinib Versus Placebo or Adalimumab in Rheumatoid Arthritis: A Randomized, Double-Blind, Phase II Trial (ANDES Study)

Arthritis Rheumatol. 2020 Sep; 72(9): 1435–1446.

In this randomised phase II trial with MTX treatment-refractory RA patients, greater efficacy was observed with fenebrutinib 150 mg once daily or 200 mg twice daily compared to placebo, while response rates were numerically similar to those observed with adalimumab. BTK inhibitors have demonstrated clinical efficacy in B cell malignancies and multiple sclerosis, although there is limited clinical evidence of its efficacy in RA. Fenebrutinib (FEN) an orally active and selective non-covalent inhib...

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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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December 2019

Highlights of 2019

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

2019 was another remarkable year in cytokine signalling. We can be optimistic that clinical practice for inflammatory arthritis will continue to improve, with promising long-term safety data supporting the use of established JAK inhibitors; tofacitinib and baricitinib, in addition to exciting phase III clinical data for filgotinib and newly approved upadacitinib. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respecti...

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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

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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