Scroll through to explore how the IL-23p19 inhibitor TREMFYA^® helps patients by treating the cause of inflammation in psoriatic arthritis.

The entheses are thought to be the cardinal site of inflammation in spondyloarthropathies including psoriatic arthritis.¹

Repeated microdamage from mechanical stress within the enthesis triggers an inflammatory response.¹

Chronic enthesitis is a hallmark feature of PsA and one that differentiates it from other arthropathies.²

Let's have a closer look at the effects of pathogenic IL-23 overproduction on a joint.^1-6

IL-23 is produced by a variety of activated myeloid cells including macrophages and dendritic cells.

These may be resident cells that permanently reside in the tissue or infiltrating cells that migrate to the tissue during inflammation.

IL-23 is a heterodimetric cytokine consisting of a p40 and a p19 subunit which plays a regulatory role in the IL-23/IL-17 axis.

IL-23 induces the differentiation of naïve T cells into Th17 T helper cells.

Th17 T helper cells produce the pro-inflammatory interleukin IL-17.

This promotes the production of other inflammatory molecules.

These include IL-8, IL-6, TNF-α, RANKL and metalloproteases.

Dysregulation of IL-23 results in pathogenic overactivation of the IL-23/IL-17 axis which can cause chronic inflammation within the enthesis.

Animal models have demonstrated that inflammation in the enthesis can subsequently spread to the adjacent synovium.

IL-17 targets a variety of cells in the joint including endothelial cells, fibroblasts, macrophages, osteoblasts and osteoclasts.

Endothelial cells

Fibroblasts

Macrophages

Osteoblasts

Osteoclasts

This leads to the production of inflammatory cytokines.

Chronic inflammation within the joint results in synovitis and bone erosion.

Other signs of psoriatic disease

Nail pitting is a hallmark
of psoriatic disease and is
thought to be a predictor
of PsA development.

Enthesitis of the extensor digitorum tendon, which is anatomically close to the nail root, is associated with nail pitting.

TREMFYA mechanism of action^7-8

TREMFYA is a first-in-class fully human anti-IL-23 monoclonal antibody that binds to the p19 subunit of the IL-23 with high selectivity and specificity.

TREMFYA binds to the p19 subunit of IL-23, preventing IL-23 from binding to receptors on the surface of naïve T cells.

In turn, this prevents T cell differentiation and proliferation, stopping the release of downstream inflammatory molecules.

PsA patients treated with TREMFYA had a significant reduction in serum levels of Th17 effector cytokines and acute inflammatory molecules.

Sustained joint efficacy^†

^†1 in 2 TREMFYA patients with ACR50 at Week 100^a9

Patients with ACR20, ACR50 & ACR70 response over 2 years (NRI)

Adapted from McInnes et al. 2021⁹

^aBionaïve 8-weekly dose PsA patients (N=248)⁹

Relief across PsA domains^‡

^‡Enthesitis

70%

of TREMFYA patients with full resolution of enthesitis at 2 years^b9

^‡Dactylitis

83%

of TREMFYA patients with full resolution of dactylitis at 2 years^b9

^‡Axial PsA

40%

of TREMFYA patients achieved BASDAI50 at Week 24 vs 19% of placebo (P=0.0054)^c10

^‡Psoriasis

53%

of TREMFYA PsA patients with PASI100 at 2 years^d9

^b8-weekly dose TREMFYA PsA patients with dactylitis (N=160) and/or enthesitis (N=230) at baseline. Per the preplanned statistical analysis plan, resolution of dactylitis and enthesitis data were combined across DISCOVER-1 and DISCOVER-2 as major secondary endpoints in the US testing procedure⁹

^cAmong 8-weekly TREMFYA (N=84) and placebo (N=110) PsA patients with investigator assessed axial PsA and evidence of sacroiliitis at baseline. Post hoc analysis of DISCOVER-1 and DISCOVER-2 population¹⁰

^dAmong bionaïve 8-weekly TREMFYA PsA patients with BSA ≥3% and IGA ≥2 at baseline (N=176)⁹

A safety profile that gives you confidence^#

^#Safety events over 2 years in TREMFYA PsA patients^e9

SAE

6.1

Per 100 PY^e9

MACE

No q8w patients experienced a MACE over 2 years^e9

Serious Infection

2.2

Per 100 PY^e9

Malignancy

One malignancy (melanoma in situ) reported over 2years^e9

^eBionaïve 8-weekly dose PsA patients (N=248)⁹

Improve daily life for PsA patients*

^*64%

of bionaïve 8-weekly dose patients with a baseline HAQ-DI >0.35 points had an improvement of >0.35 points at week 100 (N=228)⁹

^*63%

of bionaïve 8-weekly dose patients reported an improvement in physical function at Week 100, as measured by SF-36 PCS (N=248)⁹

^*42%

of bionaïve 8-weekly dose patients reported an improvement in mental wellbeing at Week 100, as measured by SF-36 MCS (N=248)⁹

PBS Information: Authority Required. Refer to PBS Schedule for full details. Please refer to Product Information before prescribing. Product Information is available from www.janssen.com.au/TREMFYA_PI

ACR20, American College of Rheumatology 20% response; ACR50, American College of Rheumatology 50% response; ACR70, American College of Rheumatology 70% response; BASDAI50, Bath Ankylosing Spondylitis Disease Activity Index 50% response; BSA, body surface area; HAQ-DI, Health Assessment Questionnaire-Disability Index; IGA, Investigator Global Assessment; IL, interleukin; MACE, major adverse cardiac event; MCS, Mental Component Score; NRI, non-responder imputation; PCS, Physical Component Score; PsA, psoriatic arthritis; PY, patient years; q8w, every 8 weeks; SAE, serious adverse events; SF-36, 36-Item Short Form Survey; TNF, tumour necrosis factor.

1. Bridgewood C, et al. Immunol Rev. 2020; 294(1): 27–47. 2. Kaeley GS, et al. Semin Arthritis Rheum. 2018; 48(1): 35–43. 3. Vecellio M, et al. Front Immunol. 2021; 11: 596086. 4. Suzuki E, et al. Autoimmun Rev. 2014; 13(4-5): 496–502. 5. Tsukazaki H, et al. Int J Mol Sci. 2020; 21(17): 6401. 6. Sherlock JP, et al. Nat Med. 2012; 18(7): 1069–1076. 7. Mease PJ, et al. Lancet. 2020; 395(10230): 1126–1136. 8. Sweet K, et al. RMD Open. 2021; 7(2): e001679. 9. McInnes IB, et al. Arthritis Rheumatol. 2022; 74(3): 475–485. 10. Mease PJ, et al. Lancet Rheum. 2021; 3(10): E715–E723.

©Janssen 2022. ^®Registered trademark of Janssen-Cilag Pty Ltd. ABN 47 000 129 975. 1-5 Khartoum Road, Macquarie Park NSW 2113. Telephone 1800 226 334. CP-303615 McCann Health. JATR2696M. April 2022.

Discover how Tremfya works

Let's have a closer look at the effects of pathogenic IL-23 overproduction on a joint.1-6

Other signs of psoriatic disease

TREMFYA mechanism of action7-8

Sustained joint efficacy†

Relief across PsA domains‡

‡Enthesitis

‡Dactylitis

‡Axial PsA

‡Psoriasis

A safety profile that gives you confidence#

SAE

6.1