Publications

Contribution of a European-Prevalent Variant Near CD83 and an East Asian-Prevalent Variant Near IL17RB to Herpes Zoster Risk in Tofacitinib Treatment: Results of Genome-Wide Association Study Meta-Analyses

Arthritis Rheumatol. 2021;73(7):1155–66

Bing N,

Zhou H,

Chen X,

Hirose T,

Kochi Y,

Tsuchida Y,

Ishigaki K,

Sumitomo S,

Fujio K,

Zhang B,

Valdez H,

Vincent MS,

Martin D,

Clark JD.

Genetic analysis of tofacitinib-treated subjects with RA or PsO identified multiple loci associated with increased herpes zoster (HZ) risk.It is well known that HZ risk is elevated in subjects with RA compared with the general population, and that treatment with JAK inhibitors may result in increased risks compared with TNFi and other bDMARD treatments. To this end, Bing, et al. used genome-wide association studies to identify genetic factors associated with an increased risk/faster onset of HZ ...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry

Ann Rheum Dis. 2021 May 28. DOI: 10.1136/annrheumdis-2021-220418

Sparks JA,

Wallace ZS,

Seet AM,

Gianfrancesco MA,

Izadi Z,

Hyrich KL,

et al.

Results from the COVID-19 Global Rheumatology Alliance physician registry show that people with RA using rituximab or JAKi, at COVID-19 onset, are more likely to experience poor COVID-19 outcomes, ranging from hospitalisation to death, compared with use of TNFi.The ongoing COVID-19 pandemic has had a significant impact on people with RA, many of whom are treated with b/tsDMARDs. To help address some of the knowledge gaps around the influence of b/tsDMARDs on COVID-19 outcomes, Sparks, et al. ana...

Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study

Wells AF, et al. Rheumatol Ther. 2021. Epub ahead of print. DOI: 10.1007/s40744-021-00317-9.

Wells AF,

Jia B,

Xie L,

Valenzuela GJ,

Keystone EC,

Li Z,

Quebe AK,

Griffing K,

Otawa S,

Haraoui B.

Analysis by Wells, et al. demonstrates long-term efficacy and tolerability of baricitinib 2 mg daily for up to 120 weeks in patients with rheumatoid arthritis.Using data from two completed phase III studies, RA-BEAM (csDMARD-IR patients) and RA-BEACON (TNFi-IR patients), and one ongoing long-term extension study (RA-BEYOND), results demonstrated that the long-term maintenance of clinically relevant treatment goals, including LDA, remission and normative physical function, is achievable with bari...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• LTE,
• Phase 3

Comparative efficacy and safety of secukinumab, ixekizumab, and tofacitinib in patients with active psoriatic arthritis showing insufficient response to tumor necrosis factor inhibitors

Int J Clin Pharmacol Ther. 2021. Epub ahead of print.

Song GG,

Lee YH.

Bayesian network meta-analysis of randomised controlled trials (RCTs) highlights the effectiveness of secukinumab, ixekizumab, and tofacitinib in patients with psoriatic arthritis (PsA) and an inadequate response to tumour necrosis factor inhibitors (TNFi).There is a current need for therapies with alternative mechanisms of actions to DMARDs and TNFi, for the significant proportion of patients with PsA who insufficiently respond to these therapies. While RCTs for therapies such as secukinumab a...

Keywords:

• JAK,
• IL-17,
• Secukinumab,
• Tofacitinib,
• Efficacy,
• Safety

Risk of venous thromboembolism associated with tofacitinib in patients with rheumatoid arthritis: a population-based cohort study

Rheumatology (Oxford). 2021 Mar 22:keab294. Epub ahead of print. DOI: 10.1093/rheumatology/keab294

Desai RJ,

Pawar A,

Khosrow-Khavar F,

Weinblatt ME,

Kim SC

A population-based cohort study of 87,653 RA patients has found no evidence for an increased risk of venous thromboembolism (VTE) for tofacitinib, versus TNFis, in patients with RA.The introduction of JAKinibs, almost a decade ago, has provided an important oral option for the treatment of RA. However, in recent years, a safety concern, relating to incidence of VTE after treatment, has emerged. Consequently, both the US and European regulatory authorities now recommend caution for use of tofacit...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Real-World

Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study

Ann Rheum Dis 2021;80:96–102.

Pappas DA,

St John G,

Etzel CJ,

Fiore S,

Blachley T,

Kimura T,

Punekar R,

Emeanuru K,

Choi J,

Boklage S,

Kremer JM

RA treatment guidelines recommend a treat-to-target approach guided by disease stage and treatment history, yet the optimal sequence of different treatment modalities has not been established. Data from Corrona – were used to evaluate the comparative effectiveness of TNFi versus non-TNFi bDMARDs and tsDMARDs as first-line treatment following csDMARD failure. Results support RA guidelines recommending individualised care based on clinical judgement and consideration of patient preference.The stud...

Keywords:

• Real-World

Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

Ann Rheum Dis 2020; doi:10.1136/annrheumdis-2020-21841220

Fleischmann RM,

Blanco R,

Hall S,

Thomson GTD,

Van den Bosch FE,

Zerbini C,

Bessette L,

Enejosa J,

Li Y,

Song Y,

DeMasi R,

Song I-H

Both ACR and EULAR recommend adding a biologic or targeted synthetic DMARD in patients who do not achieve treatment goals at follow-up. Findings indicated that an immediate switch in mechanism of action (from JAKi to TNFi and vice versa) following treat-to-target principles is feasible with minimal risk of flare regardless of whether patients are switched due to non-response or incomplete-response.SELECT-COMPARE followed treat-to-target principles to examine the efficacy of switching in two pati...

Keywords:

• JAK,
• TNF,
• Updacitinib,
• Adherence,
• Switching

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

Winthrop KL,

Citera G,

Gold D,

Henrohn D,

Connell CA,

Shapiro AB,

Shi H,

Onofrei AM,

Pappas DA,

Schulze-Koops H

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...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Real-World,
• 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

Pharmacological Treatment of Psoriatic Arthritis: A Systematic Literature Research for the 2019 Update of the EULAR Recommendations for the Management of Psoriatic Arthritis

Annals of the Rheumatic Diseases 2020;79:778-786

Kerschbaumer A,

Smolen JS,

Dougados M,

De Wit M,

Primdahl J,

McInnes I,

Van Der Heijde D,

Baraliakos X,

Falzon L,

Gossec L

This SLR reviewed data on pharmacological treatment of PsA. Findings informed the 2019 EULAR taskforce when updating recommendations for PsA management. Overall, no new safety signals were reported. Encouragingly, LTEs of JAKi did not report any venous thromboembolic events or PEs. Efficacy was demonstrated for a range of bDMARD and tsDMARD therapies in various disease domains. Efficacy varied between PsA manifestations and between therapies. Observational data demonstrated efficacy when switchi...

Keywords:

• EULAR