Lymphocyte receptor and cytokine modulators

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Rituximab MabThera, Truxima, Rixathon

Pharmacological Group: Chimeric anti-CD20 monoclonal antibody (immunosuppressant).

Mechanism of Action: It specifically binds to the transmembrane antigen CD20, expressed on the surface of pre-B and mature B lymphocytes (but absent in hematopoietic progenitor cells and mature antibody-secreting plasma cells). Binding induces cell lysis of B lymphocytes through three parallel mechanisms: antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct induction of cell apoptosis.

Black Box: HBV Reactivation and PML Prophylaxis

Hepatitis B Monitoring: Rituximab can trigger a fulminant reactivation of HBV. It is mandatory to request complete serological screening (HBsAg, anti-HBc) before the first dose. In anti-HBc carriers with or without positive HBsAg, prophylaxis should be started with concomitant entecavir or tenofovir and maintained for up to one year after stopping rituximab.
PML: PML should be suspected in the event of any new or progressively worsening neurological deficit (cognitive impairment, hemiparesis, dysarthria). Diagnosis by PCR for JC virus in cerebrospinal fluid.

Dosage in Rheumatoid Arthritis and Premedication

Guideline: A cycle consisting of two 1000 mg IV infusions spaced exactly two weeks apart. Repeat the cycle every 6 months according to response.
Mandatory Premedication: 100 mg of IV methylprednisolone administered 30 minutes before each infusion to minimize cytokine release syndrome, along with antipyretics (paracetamol) and oral antihistamines.

Pregnancy: Causes depletion of fetal B lymphocytes. Use only if the benefit outweighs the risk Breastfeeding: Not recommended Fingolimod Gilenya

Pharmacological Group: Sphingosine-1-phosphate (S1P) receptor modulator, selective immunosuppressant.

Mechanism of Action: It is actively metabolized in vivo by sphingosine kinase to form fingolimod-phosphate, an analogue of sphingosine-1-phosphate (S1P). It acts as a functional modulator of S1P type 1 (S1P₁) receptors located on lymphocytes. Initially it acts as an agonist, but persistently induces the internalization and proteasomal degradation of the receptor. Without functional S1P₁ receptors, lymphocytes lose the ability to respond to the chemotactic output signal from the lymph nodes, becoming sequestered in secondary lymphoid tissue. This dramatically reduces the infiltration of autoreactive T and B lymphocytes into the central nervous system, preserving residual peripheral immune homeostasis.

Critical Monitoring of the First Dose (Fingolimod)

Cardiac Risk: Fingolimod induces a transient decrease in heart rate due to the activation of S1P receptors coupled to acetylcholine-activated potassium channels in the cardiac atrium.
Safety Protocol: All patients must undergo continuous monitoring with continuous electrocardiogram (ECG) for at least 6 hours after receiving the first dose. Heart rate and blood pressure should be recorded every hour. In the event of symptomatic bradycardia, second-degree AV block or QTc prolongation, monitoring will be prolonged until complete resolution.

Adult Dosage and Contraindications

Dose: 0.5 mg PO once daily continuously.
Absolute Contraindications: Patients with recent myocardial infarction (<6 months), unstable angina, stroke, decompensated heart failure, second or third degree AV block, or sick sinus syndrome without a functioning pacemaker. Avoid with strong CYP3A4 inducers.

Pregnancy: Highly teratogenic. Suspend 2 months before planning pregnancy Breastfeeding: Contraindicated