Rebif
Rebif (Interferon‑β‑1a)
Generic Name
Rebif (Interferon‑β‑1a)
Mechanism
- Cell‑surface receptor binding: Binds the ubiquitously expressed interferon‑α/β receptor (IFNAR1/2) on leukocytes and glial cells.
- JAK‑STAT signaling: Triggers the Janus‑activated kinase (JAK) pathway → phosphorylation of STAT1/STAT2 → formation of ISGF3 complex → transcription of interferon‑stimulated genes (ISGs).
- Immunomodulation
- ↓ Th1/Th17 pro‑inflammatory cytokines (IL‑2, IFN‑γ, GM‑CSF).
- ↑ IL‑10 and TGF‑β through regulatory T‑cell promotion.
- ↓ adhesion of leukocytes to endothelial cells (reduces CNS infiltration).
- Neuroprotective effects: Enhances oligodendrocyte progenitor proliferation and remyelination via upregulation of neurotrophic factors.
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Pharmacokinetics
| Parameter | Details |
| Route | Subcutaneous injection |
| Bioavailability | ~30 % after SC injection |
| Peak Concentration (Tmax) | 4–6 h post‑dose |
| Half‑life | 5–20 h (dose‑dependent) |
| Metabolism | Proteolytic cleavage; not hepatic enzyme‑mediated |
| Excretion | Renal (urine) and fecal (via biliary excretion) |
| Special Populations | No dose adjustment required for renal impairment; cautious use in hepatic disease |
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Indications
- Relapsing‑Remitting Multiple Sclerosis (RRMS) – first‑line disease‑modifying therapy for new or relapsing disease.
- Secondary Progressive MS with active disease – evidence of relapse or MRI activity.
- Pediatric RRMS (≥12 y, weight ≥35 kg) – FDA‑approved in certain jurisdictions.
*Not indicated for primary progressive MS without relapses.*
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Contraindications
| Category | Detail |
| Contraindications |
• Hypersensitivity to interferon‑β or excipients • Known antibodies to interferon‑β (neutralizing) |
| Warnings |
• Pregnancy: Category B (animal studies show no teratogenicity; limited human data). Counsel patients. • Severe infection: may exacerbate sepsis or viral disease. • Lymphopenia/immune suppression: can precipitate opportunistic infections. • Thromboembolic disease: increased risk of venous thrombosis. |
| Precautions | Full vaccination status recommended (influenza, pneumococcal). Monitor for anaphylaxis during first 30 min of injection. |
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Dosing
| Phase | Dose | Schedule | Notes |
| Loading | 30 µg SC | Every other day for 8 weeks (1 dose/2 days) | Improves early efficacy. |
| Maintenance | 30 µg SC | Every other day, continuously | Continue until disease control or switch. |
| Reintroduction | 30 µg SC | Every other day | After suspension >12 months, repeat loading dose. |
Administration Tips
• Inject into the front thigh, abdomen, or upper arm (avoid sites with trauma or scarring).
• Use a 1‑cm (½”) needle; rotate sites to reduce skin reactions.
• Aspirate lightly before injection (optional).
• Dispose of needles in a puncture‑proof container.
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Adverse Effects
| Category | Examples | Frequency (clinical trials) |
| Common | Injection‑site reactions (pain, erythema, induration), flu‑like symptoms (fever, myalgia, chills), headache, fatigue, rash | 20–70 % |
| Serious | Hepatotoxicity (ALT/AST ↑ ≥ 3× ULN), acute demyelinating encephalomyelitis (ADEM), progressive multifocal leukoencephalopathy (PML), myositis with CK ↑ ≥ 10× ULN, severe allergic reactions (anaphylaxis) | < 1 % |
| Rare | Lymphoma (reported in long‑term users), thyroiditis | < 0.1 % |
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Monitoring
| Parameter | Frequency | Rationale |
| CBC with differential | Baseline, month 1, then every 3 months | Detect anemia, neutropenia, thrombocytopenia. |
| Liver function tests (AST, ALT, ALP, bilirubin) | Baseline, month 1, then every 3 months | Monitor hepatotoxicity. |
| Creatine kinase (CK) | Baseline, month 1, then every 6 months | Early detection of myositis. |
| Serum phosphate & calcium | Baseline, every 6 months | Rare hypophosphatemia reported. |
| Vaccinations | Prior to initiation | Influenza, pneumococcal, HPV (if indicated). |
| Anti‑interferon antibodies | At clinical discretion | Neutralizing antibodies may reduce efficacy. |
| MRI with contrast | Every 6–12 months | Evaluate disease activity. |
| PML screening | Baseline, annually | Though rare, risk present. |
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Clinical Pearls
- Loading vs. No‑Loading: A loading phase accelerates drug levels, leading to faster relapse reduction; patients often perceive early benefit.
- Injection‐site vigilance: Moderate‑to‑severe reactions often diminish after 4–6 weeks; if persistent >2 weeks, consider changing sites or needle length.
- Flu‑like reactions: Common in the first 24 h; prophylactic acetaminophen oruprofen may attenuate symptoms but use cautiously if liver function is already abnormal.
- Neutralizing antibodies: Their presence drops remission rates; switch to a natalizumab, fingolimod, or other agent if antibodies > 25 % neutralizing activity.
- Vaccinations: Live vaccines are contraindicated during therapy due to immunomodulation; passive immunization may be considered.
- Pregnancy counseling: While no teratogenicity signals, discontinuation during pregnancy is advised unless disease activity poses greater risk.
- PML risk: Highest in patients with prior exposure to natalizumab or prolonged treatment > 36 months; maintain baseline and annual MRI.
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• Key Takeaway: Rebif improves RRMS control through immune modulation, with a favorable safety profile when monitored properly. Adherence to dosing, site rotation, and surveillance of laboratory parameters ensures optimal therapeutic outcomes.