Qlosi
Qlosi
Generic Name
Qlosi
Mechanism
- Selective JAK‑1 inhibition:
- Blocks cytokine‑mediated intracellular signaling by preventing phosphorylation of STAT proteins downstream of IL‑12, IL‑23, and IFN‑γ receptors.
- Reduces keratinocyte hyperproliferation and Th17‑driven inflammation without affecting JAK2‑ or JAK3‑dependent pathways, thereby preserving erythropoiesis and immune competence.
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Pharmacokinetics
| Parameter | Value | Comments |
| Absorption | Peak plasma conc. (Cmax) within 1–2 h; ~95 % bioavailability | Food increases Cmax by ~20 %, but no dose adjustment required. |
| Distribution | Protein binding 68 %; mean volume of distribution 74 L | Cerebrospinal fluid penetration minimal; not expected to cause central nervous system side effects. |
| Metabolism | Hepatic CYP3A4/2C19 (≈80 %) → inactive metabolites | Concomitant strong CYP3A4 inhibitors (ketoconazole, clarithromycin) ↑ plasma exposure 3‑fold. |
| Elimination | Renal excretion ~30 % unchanged; hepatic route majority | Dose adjustment recommended in CKD stage 4–5 or end‑stage renal disease. |
| Half‑Life | 8–12 h | Allows once‑daily dosing. |
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Indications
- Plaque‑style psoriasis (moderate to severe) – 100 mg once daily.
- Psoriatic arthritis (moderate to severe) – 100 mg once daily.
*Off‑label* use has been explored for alopecia areata and atopic dermatitis, with encouraging early‑phase data.
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Contraindications
| Category | Details |
| Absolute contraindications | Active tuberculosis, untreated latent TB, uncontrolled infection, pregnancy (category X). |
| Relative contraindications | Uncontrolled cardiovascular disease (CAD ≥3 mg/dL LDL, uncontrolled HTN), concurrent use of potent CYP3A4 inhibitors or inducers. |
| Warnings | ↑Risk of infections (herpes zoster, opportunistic infections), ↑risk of thrombosis, potential for dyslipidemia. |
| Precautions | Monitor CBC, LFTs, lipid panel, and infection markers regularly. Counsel patients on signs of infection and to avoid live vaccines during therapy. |
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Dosing
- Starting dose: 100 mg oral tablet once daily.
- Titration: Not required; dose may be increased to 200 mg daily in some psoriasis indications if inadequate response after 12 weeks.
- Duration: Long‑term therapy is approved; treatment interruption >4 weeks requires re‑induction titration.
- Administration: Take with or without food; avoid grapefruit juice and strong CYP3A4 substrates.
- Discontinuation: Stop abruptly if severe infection or laboratory abnormality occurs. Gradual taper may be advised for psoriatic arthritis flare.
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Adverse Effects
| Common (≥5 %) | Serious |
| ↑lipid levels (↑LDL, ↑TG) | Serious infections (TB, candidiasis) |
| Headache, dizziness | Thromboembolic events (DVT, PE) |
| Nasopharyngitis | Cytopenias (neutropenia, lymphopenia) |
| Upper respiratory tract infection | Hepatotoxicity |
| Mild GI upset (nausea, diarrhea) | Rhabdomyolysis (rare) |
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Monitoring
| Parameter | Frequency | Goal |
| CBC with diff. | Baseline, then monthly for first 3 months, then every 3 months | ANC > 1.5 × 10⁹/L; platelets > 100 × 10⁹/L |
| LFTs | Baseline, then every 3 months | AST/ALT < 2 × ULN |
| Lipid panel | Baseline, 6 weeks, then every 6 months | LDL 30 mL/min/1.73 m² |
| TB screening (tuberculin skin test / IGRA) | Baseline, then annually | No active disease |
| Patient diary (infection signs) | Ongoing | Early detection of opportunistic infections |
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Clinical Pearls
1. Rapid Titration? – Unlike traditional biologics, Qlosi’s oral route allows a single‑step switch from another JAK‑1 agent without overlap, minimizing myelosuppression risk.
2. Teratogenicity Alert – Strongly discouraged in pregnancy; avoid in women of childbearing age unless effective contraception is ensured.
3. Drug‑Drug Interactions – Even moderate CYP3A4 inhibitors (e.g., itraconazole, erythromycin) can raise Qlosi levels; consider dose reduction or alternative antimicrobials.
4. Thromboembolism Risk – Monitor for signs of DVT/PE even after the first 6 months; consider baseline D-dimer if high cardiovascular risk exists.
5. Gastro‑intestinal Persistence – The drug’s low CNS penetration reduces the risk of central side effects seen with other JAK inhibitors.
6. Reactivation of Past HZ – Vaccinate patients with the recombinant zoster vaccine (Shingrix) ≥2 months prior to initiation to reduce shingles risk.
7. Renal Adjustments – In CKD stage 3 (eGFR 30–59 mL/min/1.73 m²) the standard dose is maintained, but in stage 4–5 or dialysis consider reducing to 50 mg daily until further safety data are available.
8. Monitoring Frequency – A pragmatic approach: CBC and LFTs at baseline, 4 weeks, then every 8 weeks for the first 6 months, then quarterly, can catch emerging cytopenias early.
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• Key Takeaway: Qlosi offers an oral, highly selective JAK‑1 blockade with reduced hematologic toxicity relative to first‑generation JAK inhibitors, making it attractive for long‑term management of plaque psoriasis and psoriatic arthritis, provided appropriate monitoring and infection prophylaxis are in place.