Publications

Relative Efficacy and Safety of Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib in Comparison to Adalimumab in Patients with Active Rheumatoid Arthritis

Z Rheumatol. 2020 DOI: 10.1007/s00393-020-00750-1

Lee YH,

Song GG

This Bayesian network meta-analysis, comparing the relative efficacy and safety of JAK inhibitors, determined BARI 4mg + MTX and UPA 15mg + MTX were the most effective. The analysis included 5451 patients with an inadequate response to MTX and active RA, from four RCTs. Relative effects were converted into a probability allowing each treatment to be ranked. BARI and UPA had significantly higher ACR20 response rates than ADA 40mg + MTX whilst TOF 5mg and FIL 200mg had comparable ACR20 response ra...

Keywords:

• JAK,
• Baricitinib,
• Tofacitinib,
• Upadacitinib,
• Safety,
• Efficacy

Long-term Effectiveness of Live Herpes Zoster Vaccine in Patients with Rheumatoid Arthritis Subsequently Treated with Tofacitinib

Ann Rheum Dis. 2020 10.1136/annrheumdis-2019-216566

Winthrop KL,

Wouters A,

Choy EH,

Chen C,

Biswas P,

Wang L,

Soma K,

Needle E,

Valdez H,

Rigby WFC

The results of ORAL Sequel suggest that the live zoster vaccine (LZV) may not provide adequate long-term protection in patients with RA receiving TOF. This LTE study enrolled 100 patients with RA, 14 weeks post LZV vaccination. Patients received either TOF 5 mg BID, or TOF 10 mg BID in addition to any background csDMARDs. Incidence rates and 95% CIs for HZ post-vaccination were calculated based on time to first event. Short-term varicella zoster vaccine (VZV) specific immunity was evaluated at ...

Keywords:

• JAK,
• Tofacitinib,
• Vaccination

IgA Vasculitis Developed as an Adverse Effect of Tofacitinib Taken for Rheumatoid Arthritis

Intern Med. 2020;59(6):817-821

Itoh I,

Kasuno K,

Yamamoto C,

Takahashi N,

Shimizu H,

Ojima T,

Hayashi S,

Kimura H,

Iwano M

Nephrotoxicity is a key side effect of NSAIDs and DMARDs used to treat RA, while biologics can reportedly cause proliferative glomerulonephritis or crescentic glomerulonephritis. This report reviews a patient on TOF presenting IgA vasculitis as an adverse effect that fully resolved following termination of TOF.Drug induced IgA vasculitis has been previously described for anti-TNFɑ therapies, but this is the first report with JAK inhibitor therapy. This is a case report of a 67-year old woman wit...

Keywords:

• JAK,
• Tofacitinib,
• Safety

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

Baricitinib Exposure During Pregnancy in Rheumatoid Arthritis

Ther Adv Musculoskelet Dis. 2020;12:1759720X19899296

Costanzo G,

Firinu D,

Losa F,

Deidda M,

Barca MP,

Del Giacco S.

Broad and focused studies are required to have an insight of safety for small molecules, such as JAK inhibitors in the case of accidental exposure before or during pregnancy.This case study’s objective describes a case report of a 43-year-old woman affected by RA who became pregnant during BARI treatment. She has had two previous pregnancies at term without complications. After failure of bDMARDs due to loss of efficacy and adverse drug reactions, the patient was started on BARI when it became a...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Pregnancy / Fertility

Impact of Janus Kinase Inhibition with Tofacitinib on Fundamental Processes of Bone Healing

Int J Mol Sci 2020;21:865

Gaber T,

Brinkman ACK,

Pienczikowski J,

Diesing K,

Damerau A,

Pfeiffenberger M,

Lang A,

Ohrndorf S,

Burmester G-R,

Buttgereit F,

Hoff P

TOF demonstrated a dose-dependent promotion of human mesenchymal stromal cell (hMSC) recruitment under hypoxia, while inhibiting recruitment under normoxia. TOF also dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. As people age, they are more likely to suffer from fractures and delayed bone healing, as well as degenerative joint diseases or osteoporosis. Bone metabolism and fracture healing may be negatively affected by underlyin...

Keywords:

• JAK,
• Tofacitinib,
• Bone

JAK Inhibition Increases Bone Mass in Steady state Conditions and Ameliorates Pathological Bone Loss by Stimulating Osteoblast Function

Sci Transl Med 2020;12(530):pii: eaay4447

Adam S,

Simon N,

Steffen U,

Andes FT,

Scholtysek C,

Müller DIH,

Weidner D,

Andreev D,

Kleyer A,

Culemann S,

Hahn M,

Schett G,

Krönke G,

Frey S,

Hueber AJ

JAKi significantly increased osteoblast function but showed no direct effects on osteoclasts.JAK signalling has emerged as an important therapeutic target for inflammatory disease, and the immunomodulation of JAK inhibition is well defined. Less well understood is the influence of this new class of drugs on bone homeostasis. This is important, as cytokine dysregulation triggers bone loss, and periarticular erosions contribute to the pathogenesis of RA. This study investigated the effect of BARI ...

Keywords:

• JAK,
• Bone

EULAR Recommendations for the Management of Rheumatoid Arthritis – 2019 Update and Consensus Statement on JAKinibs

Ann Rheum Dis. 2020 Jan 22. pii: annrheumdis-2019-216655.

Smolen JS,

Landewé RBM,

Bijlsma JWJ,

Burmester GR,

Dougados M,

Kerschbaumer A,

McInnes IB,

Sepriano A,

et al.

The EULAR recommendations for the management of RA have become increasingly useful in providing rheumatologists, patients, payers and other stakeholders with the evidence-based guidance and views of experts on the optimal use and sequence of pharmaceutical therapies in patients with RA. Over the course of the last decade, the evolution of the treatment landscape has already required two updates. The release of the new addition updates the 2016 recommendations.An international task force consider...

Keywords:

• EULAR

Filgotinib, a JAK1 Inhibitor, Modulates Disease Related Biomarkers in Rheumatoid Arthritis: Results from Two Randomized, Controlled Phase 2b Trials

Rheumatol Ther. 2020 DOI: 10.1007/s40744-019-00192-5

Tarrant JM,

Galien R,

Wanying L,

Goyal L,

Pan Y,

Hawtin R,

Zhang W,

Van der Aa A and Taylor PC

In this study examining the effect of FIL on a panel of biomarkers, FIL down-modulated several key inflammatory mediators of signalling pathways in RA - independent of MTX background therapy. This confirmed the strong network effects of the JAK1 node in autoimmunity, matrix and cartilage degradation, angiogenesis, and leukocyte adhesion and recruitment. Biomarkers key to RA pathophysiology were measured at baseline, Wk4 and Wk12 in FIL 100 mg, FIL 200 mg or PBO treatment groups from two phase 2b...

Keywords:

• JAK,
• Filgotinib,
• Phase 2,
• MOA,
• Biomarkers

Osteoimmunology In Rheumatoid and Psoriatic Arthritis: Potential Effects of Tofacitinib on Bone Involvement

Clin Rheumatol. 2020

Orsolini G,

Bertoldi I,

Rossini M.

Data showing that TOF can inhibit unbalanced osteoclastogenesis in RA suggests that targeting the JAK-STAT pathway can halt bone erosion, as TOF has been shown to reduce articular bone erosion in RA and PsA.The authors in this review summarise current knowledge on the relationship between the immune system and the skeleton before examining the involvement of JAK-STAT signalling in bone homeostasis while discussing the evidence on the benefit of TOF on prevention of bone involvement in RA and PsA...

Keywords:

• JAK,
• Tofacitinib,
• Basic Science