Publications

Bimekizumab versus adalimumab in plaque psoriasis

N Engl J Med 2021; 385:130–41. doi: 10.1056/NEJMoa2102388

Warren RB,

Blauvelt A,

Bagel J,

Papp KA,

Yamauchi P,

Armstrong A,

Langley RG,

Vanvoorden V,

De Cuyper D,

Cioffi C,

Peterson L,

Cross N,

Reich K

Bimekizumab was noninferior and superior to adalimumab with respect to PASI 90 response and IGA score at Week 16. Bimekizumab is a promising IL-17A/F inhibitor that has shown clinical improvement in PsO patients compared to placebo and other IL inhibitors. Warren et al. compared the safety and efficacy of bimekizumab with adalimumab in a 56-week double-blind trial.

Keywords:

• Bimekizumab,
• Efficacy,
• Phase 3,
• Safety,
• Skin

Differential Properties of Janus Kinase Inhibitors in the Treatment of Immune-mediated Inflammatory Diseases

Rheumatology (Oxford) 2023;63(2):298–308 doi 10.1093/rheumatology/kead448

Taylor PC,

Choy E,

Baraliakos X,

Szekanecz Z,

Xavier RM,

Isaacs JD,

Strengholt S,

Parmentier JM,

Lippe R,

Tanaka Y

JAKis differ in structure, which affects their inhibitory concentration for different JAKs.

This review by Taylor, et al. compares the pharmacological profiles of JAKis, including abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib, and upadacitinib.

Keywords:

• JAK,
• Basic Science,
• MOA

Guselkumab Modulates Differentially Expressed Genes in Blood of Patients with Psoriatic Arthritis: Results from Two Phase 3, Randomized, Placebo-Controlled Trials

ACR Open Rheumatol. 2023 doi: 10.1002/acr2.11589

Siebert S,

Sweet KM,

Ritchlin CT,

Hsia EC,

Kollmeier AP,

Xu XL,

Seridi L,

Song Q,

Gao S,

Chen W,

Miron M

Whole blood transcriptome profiling reveals differential gene expression in patients with active PsA from the DISCOVER-1 and DISCOVER-2 clinical studies in comparison with healthy controls.

Keywords:

• IL-23,
• Guselkumab,
• Phase 3,
• Basic Science,
• MOA

The Incidence of Opportunistic Infections in Patients with Psoriatic Arthritis Treated with Biologic and Targeted Synthetic Agents: A Systematic Review and Meta-analysis

Front Pharmacol 2022;13:992713 doi: 10.3389/fphar.2022.992713

Vassilopoulos A,

Shehadeh F,

Benitez G,

Kalligeros M,

Cunha JS,

Cunha CB,

Mylonakis E

This is the largest meta-analysis to date, assessing the risk of OIs (Opportunistic infection) in patients with PsA. In coming to this conclusion, a systematic review and meta-analysis was undertaken to estimate the incidence of OIs following treatment with b- and tsDMARDs.

Keywords:

• Safety,
• Infections,
• Review

Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis

N Engl J Med. 2022;387(8):715–726. doi: 10.1056/NEJMoa2201302

Smolen JS,

Feist E,

Fatenejad S,

Grishin SA,

Korneva EV,

Nasonov EL,

Samsonov MY,

Fleischmann RM; CREDO2 Group; CREDOZ Group.

Phase 3 trial of olokizumab, a direct inhibitor of the IL-6 ligand, demonstrates superiority to placebo with respect to an ACR20 response at week 12 and noninferiority to adalimumab (all combined with methotrexate), in patients with RA.

Keywords:

• IL-6,
• Olokizumab,
• Phase 3

Two Phase 3 Trials of Baricitinib for Alopecia Areata

N Engl J Med. 2022. Epub ahead of print doi: 10.1056/NEJMoa2110343

King B,

Ohyama M,

Kwon O,

Zlotogorski A,

Ko J,

Mesinkovska NA,

Hordinsky M,

Dutronc Y,

Wu WS,

McCollam J,

Chiasserini C,

Yu G,

Stanley S,

Holzwarth K,

DeLozier AM,

Sinclair R,

BRAVE-AA Investigators

Phase 3 trials in patients with severe alopecia areata show that baricitinib is superior to placebo with respect to hair regrowth at 36 weeks.
Alopecia areata is characterised by nonscarring hair loss that can affect any hair-bearing site. Although mild cases of this emotionally- and psychosocially-distressing autoimmune disease may resolve within 12 months, more severe forms of the disease are unlikely to remit without treatment.

Keywords:

• JAK,
• Baricitinib,
• Phase 3

JAK/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis

Clin Exp Rheumatol. 2021;39(3):668-675.

Crispino N,

Ciccia F.

The JAK/STAT pathway is receiving increasing attention in modulation of nociceptive responses, given its clear role in cytokine signalling. The authors of this review speculate that JAKinibs may have an effect on the modulation of nociception and reduction of pain.Crispino N, et al. review the impact of pain in patients with rheumatic disease and the physiological basis of modulating nociceptive pain. They examine the role of cytokines in the modulation of pain and analyse current clinical JAKin...

Keywords:

• JAK,
• Basic Science,
• MOA

Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

Front. Cell Dev. Biol. 9:630942 DOI: 10.3389/fcell.2021.630942

Estupiñán HY,

Berglöf A,

Zain R,

Smith CIE

Understanding of the B-cell receptor signalling pathway led to the identification of a suitable drug target to addresses autoimmunity and inflammation in areas such as MS, RA, pemphigus and SLE. There are currently 22 BTKis in various stages of clinical development. However, AEs such as cardiovascular and bleeding side effects, as well as rash, diarrhoea and infections have been associated with the inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain.Based on clinic...

Keywords:

• BTK,
• MOA,
• Review

JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib

Ann Rheum Dis. 2021 Mar 19:annrheumdis-2020-219012. Epub ahead of print. DOI: 10.1136/annrheumdis-2020-219012

Traves PG,

Murray B,

Campigotto F,

Galien R,

Meng A,

Di Paolo JA

The first study to combine in vitro inhibition of cytokine responses in whole blood with clinical pharmacokinetics of individual JAKinibs to model daily cytokine-mediated pharmacodynamic profiles in healthy individuals and patients with RA, has demonstrated that JAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type.Traves and colleagues have observed that JAKinibs have unique, differential effects on specific cytokine signalling pathways, dependent on cytokine stimulus, ST...

Keywords:

• JAK,
• Basic Science,
• MOA

Trial of UPA or Abatacept in Rheumatoid Arthritis

N Engl J Med 2020;383:1511–21 DOI: 10.1056/NEJMoa2008250

Rubbert‑Roth A,

Enejosa J,

Pangan AL,

Haraoui B,

Rischmueller M,

Khan N,

Zhang Y,

Martin N,

Xavier RM

In patients with refractory RA to bDMARDs, upadacitinib was found to be superior to abatacept in DAS28-CRP change from baseline and the achievement of remission at week 12.612 bDMARD-IR patients were randomised 1:1 to UPA 15 mg QD or ABA, each in combination with stable synthetic DMARDs. At Week 12, patients with <20% decrease in TJC and Swollen joint count (SJC) had background medication adjusted or added. All patients completing Week 24 were eligible to remain in an open-label, long-term exten...

Keywords:

• JAK,
• Updacitinib