Publications

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 A,

Leonardi C,

Gooderham M,

Papp K,

Philipp S,

Wu J,

Igarashi A,

Flack M,

Geng Z,

Wu T,

Camez A,

Williams D,

Langley G

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.

Keywords:

• Efficacy,
• IL-23,
• Phase 3,
• Risankizumab,
• Safety

Highlights of 2020

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

McInnes. I

2020 unfolded apace, dominated by COVID-19 - we have all had to adapt in our practice and in our knowledge base. Amid this there have continued to be a constant flow of publications and science in cytokine signaling, and as in previous years as we come the end of 2020, I will highlight some of the notable papers of the year. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respective detailed summaries below:

Keywords:

• Review

Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a systematic literature research

RMD Open 2020;6:e001374 doi:10.1136/rmdopen-2020-001374

Kerschbaumer A,

Smolen JS,

Nash P,

Doerner T,

Dougados M,

Fleischmann R,

Geissler K,

McInnes IM,

Takeuchi T,

Trauner M,

Winthrop K,

de Wit M,

Boehncke W-H,

Falzon L,

van der Heijde D

Trials of JAKi have been conducted in many therapy areas, including rheumatology, dermatology and gastroenterology. In 2019, a task force was set up to create a consensus to guide clinicians on how to use JAKi in clinical practice. This systematic literature review conducted in 2019 support this consensusIn line with EULAR’s standardised operating procedures for recommendations, a literature search was conducted in EMBASE, Medline and the Cochrane Library databases. To evaluate the efficacy of t...

Keywords:

• JAK,
• Review

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

Cohen SB,

van Vollenhoven RF,

Winthrop KL,

Zerbini CAF,

Tanaka Y,

Bessette L,

Zhang Y,

Khan N,

Hendrickson B,

Enejosa JV,

Burmester GR.

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...

Keywords:

• JAK,
• Updacitinib,
• Safety,
• Phase 3

Infections in Baricitinib Clinical Trials for Patients with Active Rheumatoid Arthritis

Annals of the Rheumatic Diseases, May 2020

Winthrop KL,

Harigai M,

Genovese MC,

Lindsey S,

Takeuchi T,

Fleischmann R,

Bradley JD,

Byers NL,

Hyslop DL,

Issa M,

Nishikawa A,

Rooney TP,

Witt S,

Dickson CL,

Smolen JS,

Dougados M

Baricitinib, an oral selective JAK1 and JAK2 inhibitor,8 demonstrated significant clinical efficacy in phase 3 RA trials. Pooled data from these trials, including a long-term extension (LTE), inform the safety profile for baricitinib, mainly to evaluate the incidence of infection in patients with active rheumatoid arthritis (RA), with a focus on serious infection, tuberculosis (TB), herpes zoster (HZ) and opportunistic infection (OI). The data collected were from eight double-blind randomised tr...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Infections

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

Annals of the Rheumatic Diseases 2020;79:760-770

Sepriano A,

Kerschbaumer A,

Smolen JS,

Van Der Heijde D,

Dougados M,

Van Vollenhoven R,

McInnes IB,

Bijlsma JW,

Burmester GR,

De Wit M,

Falzon L,

Landewé R

This SLR informed the 2019 EULAR taskforce updating recommendations for RA management. Overall, no new safety signals were reported. The known safety profile of bDMARDs was confirmed and extended to tsDMARDS. IL-6i associated lower intestinal perforation has been further confirmed, while VTE and PE concerns in JAKi treatment need further evaluation.Previous updates for the EULAR recommendations on RA pharmacological management were conducted in 2016. In this SLR safety of csDMARDs, tsDMARDs, and...

Keywords:

• Safety,
• EULAR

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

Safety Profile of Baricitinib For the Treatment of Rheumatoid Arthritis Over a Median of 3 Years of Treatment: An Updated Integrated Safety Analysis

Lancet Rheumatol 2020;2:e347–57

Genovese MC,

Smolen JS,

Takeuchi T,

Burmester G,

Brinker D,

Rooney TP,

Zhong J,

Daojun M,

Saifan C,

Cardoso A,

Issa M,

Wu W-S,

Winthrop KL

RA is a chronic, life-long disease requiring long-term treatment. As such, it is important to understand the long-term safety profile of DMARDs. In this analysis, baricitinib maintained a stable safety profile during long-term exposure. This baricitinib safety analysis included integrated data from nine Phase 3, 2, and 1b clinical trials, and one long-term extension, with data up to 360 weeks. 3700 patients were included, with maximum follow-up of almost 7 years – representing an additional 3,54...

Keywords:

• JAK,
• Baricitinib,
• Safety

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

Burmester GR,

Curtis JR,

Yun H,

FitzGerald O,

Winthrop KL,

Azevedo VF,

Rigby WFC,

Kanik KS,

Wang C,

Biswas P,

Jones T,

Palmetto N,

Hendrikx T,

Menon S,

Rojo R

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...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• Real-World