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| Primary information |
|---|
| ID | 13699 |
| Therapeutic ID | Th1426 |
| Protein Name | Guselkumab |
| Sequence | >Th1426_Guselkumab
EVQLVQSGAEVKKPGESLKISCKGSGYSFSNYWIGWVRQMPGKGLEWMGIIDPSNSYTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARWYYKPFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 143.6 |
| Chemical Formula | C6402H9864N1676O1994S42 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Mean half-life of guselkumab is approximately 15 to 18 days in subjects with plaque psoriasis [FDA Label]. |
| Description | Guselkumab is a human immunoglobulin G1 lambda (IgG1) monoclonal antibody that selectively blocks interleukin-23. IL-23 is an inflammatory cytokine that activates the CD4+ T-helper (Th17) cell pathway to mediate the inflammatory cascade that induces psoriatic plaque formation [A20357]. In clinical trials, guselkumab demonstrated improved skin clearance and symptomatic improvements in dermatological manifestations of psoriasis. Developed by Janssen, the subcutenous injection form of guselkumab was approved in July 2017 under the market name Tremfya for the treatment of adult patients with moderate-to-severe plaque psoriasis. |
| Indication/Disease | Indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. |
| Pharmacodynamics | Guselkumab is shown to reduce serum levels of IL-17A, IL-17F and IL-22 [FDA Label]. |
| Mechanism of Action | Guselkumab targets the p19 alpha subunit of IL-23. While IL-23 promotes the normal inflammatory and immune responses, the p19 and p40 subunits of IL-23 are found to be over-expressed in the condition of psoriasis and other autoimmune inflammatory skin diseases [A20357, A20359]. Guselkumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes and blocks its interaction with IL-23 receptor, which further prevents the release of other pro-inflammatory cytokines and chemokines via stimulation of immune cells such as Th17 cells [FDA Label]. Thus, guselkumab blocks the abnormally-heightened signalling of inflammatory cascades that promote epidermal abnormalities including keratinocyte hyperproliferation and psoriatic plaque formation [A20358]. |
| Toxicity | Animal studies to assess the effect of guselkumab on carcinogenesis, mutagenesis and impairment on fertility have not been conducted. When subcutaneously injected into guinea pigs, the doses of guselkumab up to 100mg/kg twice-weekly demonstrated no effects on fertility parameters [FDA Label]. |
| Metabolism | Like other human IgG monoclonal antibodies, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways [FDA Label]. |
| Absorption | Following a 100mg subcutaneous administration, the peak plasma concentration (Cmax) of guselkumab is 8.09 ± 3.68 mcg/mL which is reached after approximately 5.5 days [FDA Label]. |
| The apparent volume of distribution is 13.5 L [FDA Label]. |
| Clearance | Apparent clearance in subjects with plaque psoriasis is 0.516 L/day [FDA Label]. |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-23 subunit alpha |
| Brand Name | Tremfya |
| Company | Janssen Cilag International Nv |
| Brand Description | Janssen Cilag International Nv |
| Prescribed For | Subcutaneous |
| Chemical Name | 100 mg |
| Formulation | TREMFYA is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients [see WARNINGS AND PRECAUTIONS]. |
| Physical Appearance | upper respiratory infections, headache, injection site reactions, joint pain, diarrhea, gastroenteritis (nausea, vomiting, diarrhea, cramps, and fever), tinea infections (athlete's foot, ringworm, jock itch), and herpes simplex infections |
| Route of Administration | Tremfya is a monoclonal antibody that blocks a certain protein in the body that can cause inflammation and other immune responses. Tremfya is used to treat moderate to severe plaque psoriasis in adults. Tremfya is also used to treat active psoriatic arthritis in adults. Warnings Tremfya can weaken (suppress)... |
| Recommended Dosage | TREMFYA® is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |