Publications

Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis

Rheumatol Ther 2023;11(1):97–112 doi 10.1007/s40744-023-00621-6

Rubbert-Roth A,

Kakehasi AM,

Takeuchi T

Rates of malignancy were similar between upadacitinib, adalimumab, and MTX. They were also consistent across RA, PsA, AS and nr-axSpA. A dose-dependent increased rate of NMSC was observed with upadacitinib in RA. For RA and PsA, being older (≥65 years) and male was associated with
an increased risk of malignancy excluding NMSC.

Keywords:

• JAK,
• Malignancy,
• Updacitinib

The Risk and Predictors of Malignancies in Ankylosing Spondylitis Patients in Israel—A Retrospective Electronic Data-Based Study

J Clin Med. 2023;12(15):5153 doi: 10.3390/jcm12155153

Kagan P,

Horesh N,

Amital H,

Tsur AM,

Watad A,

Cohen AD,

Ben-Shabat N

Findings from a retrospective electronic data-based study, assessing risk of overall and site-specific malignancies for AS patients in Israel, emphasize the importance of maintaining the routine observation of patients with AS to identify the early development of cancer.

Keywords:

• Safety,
• Malignancy

JAK Inhibitors and the Risk of Malignancy: A Meta-analysis Across Disease Indications

Ann Rheum Dis. 2023;82(8):1059–1067 doi: 10.1136/ard-2023-224049

Russell MD,

Stovin C,

Alveyn E,

Adeyemi O,

Chan CKD,

Patel V,

Adas MA,

Atzeni F,

Ng KKH,

Rutherford AI,

Norton S,

Cope AP,

Galloway JB

The objective of this study was to estimate the association of JAKi with the incidence of malignancy, compared with placebo, TNFi and MTX.

Keywords:

• JAK,
• Safety,
• Malignancy,
• Review

Baricitinib Safety for Events of Special Interest in Populations at Risk: Analysis from Randomised Trial Data Across Rheumatologic and Dermatologic Indications

Adv Ther. 2023;40(4):1867–1883 doi: 10.1007/s12325-023-02445-w

Taylor PC,

Bieber T,

Alten R,

Witte T,

Galloway J,

Deberdt W,

Issa M,

Haladyj E,

De La Torre I,

Grond S,

Wollenberg A

Analysis of pooled data from the baricitinib clinical development programmes finds a low incidence rate of MACE, myocardial infarction, lung cancer, VTE, and overall mortality in patients <65 years without risk factors.

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Review

Malignancy Risk with Tofacitinib versus TNF Inhibitors in Rheumatoid Arthritis: Results from the Open-Label, Randomised Controlled Oral Surveillance Trial

Ann Rheum Dis. 2023;82(3):331–343 doi: 10.1136/ard-2022-222543

Curtis JR,

Yamaoka K,

Chen YH,

Bhatt DL,

Gunay LM,

Sugiyama N,

Connell CA,

Wang C,

Wu J,

Menon S,

Vranic I,

Gómez-Reino JJ

Results from the open-label, randomised controlled ORAL Surveillance trial find increased risk of malignancies with tofacitinib versus TNFi, highlighting the highest incidence in patients with a history of atherosclerotic cardiovascular disease or increasing cardiovascular risk.

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Malignancy

Tofacitinib and Risk of Malignancy: Results From the Safety of Tofacitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA) Study

Arthritis Rheumatol. 2022;74:1648–1659 doi: 10.1002/art.42250

Khosrow-Khavar F,

Desai RJ,

Lee H,

Lee SB,

Kim SC

Large, population-based, real-world cohort of study in patients with RA finds tofacitinib not to be associated with an increased risk of malignancies, in comparison to TNFi agents, although a numerically increased risk of malignancies was observed in older patients with risk factors for cardiovascular disease.

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Malignancy

Short- and longer-term cancer risks with biologic and targeted synthetic disease-modifying antirheumaticdrugs as used against rheumatoid arthritis in clinical practice

Rheumatology (Oxford) 2022 doi: 10.1093/rheumatology/keab570

Huss V,

Bower H,

Wadström H,

Frisell T,

Askling J; ARTIS group

Observational, nationwide cohort study finds no increased risk for cancer overall in RA patients treated with TNFis, anti-CD20 or anti-IL6.

Keywords:

• JAK,
• Safety,
• Malignancy

Cardiovascular and Cancer Risk With Tofacitinib in Rheumatoid Arthritis

N Engl J Med 2022;386:316–26. doi: 10.1056/NEJMc2202778

Ytterberg SR,

Bhatt DL,

Mikuls TR,

Koch GG,

Fleischmann R,

Rivas JL,

Germino R,

Menon S,

Sun Y,

Wang C,

Shapiro AB,

Kanik KS,

Connell CA

In this paper, Ytterberg et al. compare incidence of MACE and cancers (excluding NMSC) with tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi. They found that risk of MACE and cancer were higher with tofacitinib versus TNFi, and did not meet noninferiority criteria.This prospective head-to-head safety trial compared tofacitinib to TNFi, and was required by the FDA after increases in lipid levels and cancers were observed during tofacitinib drug development. ...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Malignancy,
• Cardiovascular

Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials

Auto Immun Highlights. 2021;12(1):8.

Solipuram V,

Mohan A,

Patel R,

Ni R.

The combination of JAK inhibitors with MTX is not associated with an increased risk of malignancy when compared to MTX alone. Although long-term studies are needed to confirm this conclusion from short-term studies. Although it is now known that patients with RA are predisposed to an increased risk of malignancy, especially malignant lymphomas, lung cancers and non-melanoma skin cancer, it remains unclear whether the combination therapy is associated with a higher risk.To this end, Solipuram, et...

Keywords:

• JAK,
• Meta Analysis,
• Safety,
• Malignancy

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