Introduction

• RITUXIMAB is an monoclonal chimeric anti-CD 20 monoclonal antibody 
• It is an effective B cell depleting

agent 

• Normally in a healthy individual the immune system works by protecting the body from infections by causing inflammation but in few the Immune system acts beyond and tries to target your own body cells instead of protecting them .
• These conditions are nothing but autoimmune disorders which react by producing self antibodies known as autoantibodies.
• So in these cases the rituximab plays a prominent role by removing or inhibiting  the B cell activity .

• Rituximab functions by binding to CD 20 on B cells which make antibodies and also inhibit antigen presentation to the cells 
• It usually takes about 6months to function and can  last upto 9 months with dosages between 2-3 weeks and continued if no side effects are encountered .

Usage in kidney disease

• Disease such as lupus nephritis/SLE
• nephrotic syndrome
• minimal change disease 
• Membranous nephropathy
• Anti-neutrophil cytoplasmic antibody associated vasculitis
• FSGS(Focal segmental Glomerulosclerosis)
• Transplantation 
• Hemolytic uremic syndrome
• Mixed essential cryoglobulinemia 

Lupus nephritis

• In lupus nephritis,the use of drug is proven effective only when the condition is refractory/severe/relapsing to the standard therapy
• Few other studies have proven that early b cell depletion at the early stages with rituximab is safe and effective.
• Results were quite good enough in both proliferative and membranous lupus nephritis
• Few histopathological studies shown an renal activity improvement after the usage
• All the mean values were decreased such as anti ds-DNA antibody ,serum ESR &C3 serum complement levels.
• It’s still a controversial choice of drug to be used as a part of conventional therapy

Nephrotic syndrome

• Especially used in steroid resistant nephrotic syndrome cases 
• May be effective in steroid refractory, resistant/calcineurin inhibitor -dependent patients ,only after withdrawal of 1 or 2 agents.
• The renal activity is better in complete remission and partial remission than non-remission which  shows worst creatinine levels
• The prognosis is not good resulting in end stage renal disease (ESRD),usually recurrence after transplantation. 
• Its use is still on hold

Membranous nephropathy 

• Similar to that of the SRNS  which usage is best in refractory or resistant cases 
• There is a significant decrease in anti-m phospholipase  receptor antibodies(A2) which is an target antigen present on glomerular podocytes
• Most of results achieved either partial or complete remission
• Treatment with rituximab ended up clinical outcomes with decreased proteinuria but an increase in albuminemia
• The renal function does not seem to change

Anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitis 

• Treatment with rituximab in ANCA associated vasculitis shows an outstanding results when compared to the conventional therapy by cyclophosphamide 
• Risk of death ,progression to ESRD and the disease relapse decreased with the usage 
• Microscopic polyangiitis and wegener’s granulomatosis comes under this group of disease

FSGS(Focal segmental Glomerulosclerosis)

• Good enough in steroid dependent but not in steroid resistant conditions
• Successful results in recurrent post transplant with plasma exchange 
• Works directly on glomerular podocytes as well as on b cells 
• Recommended for High Risk patients before transplantation to avoid recurrence

Mixed essential cryoglobulinemia 

• Monotherapy by rituximab is safe and effective drug for severe cryoglobulinemia cases with the long term followup and maintenance 
• As we know that rituximab has potential towards the b cell depletion therefore reduce the formation of cryoglobulin immune complex 
• Can be used and it is well tolerable 

Hemolytic uremic syndrome

• Effective in thrombotic thrombocytopenia -Hemolytic uremic syndrome 
• Known for better results in both resistant,relapse cases as well as in with or without willebrand factor-cleaving protease deficiency 
• The clinical profile exhibits the decreases fragmented red blood cells with elevated counts of platelet and HB post treatment 

Transplantation

• Have outstanding reports with the use of rituximab in or post Transplantation 
• Can be used for desensitization protocols,antibody mediated rejections (AMR), lymphoproliferative disorders (PTLD) as an adjunct to plasma exchange and IVIG.

Side effects 

The side effects are often encountered during first dose of infusions and last for few hours or in some may last for few days 

Usually the adverse effects are rare and mild. The frequently observed side effects  include

• Fever,chills
• Back pain,bodyache 
• Chest pain
• Bloating/swelling up of face
• Black stool
• Blood in urine
• Cough
• Difficulty during breathing
• Confusion,drowsiness
• Headache
• Nausea, vomiting
• Sore Throat
• Weakness
• Bleeding 
• Unexplained Weight gain or loss 
• Sweating during night 
• Dry mouth,bleeding gums
• Skin rashes ,tingling sensation 
• Thinning of hair 

Less common are 

• Anxiety
• Lightheadedness
• Blisters over skin surface
• Joint pains
• Loss of appetite 
• Stabbing pain 
• Weakness
• Unsteadiness
• Speech trouble
• Change in mood or behavior
• Eye sight loss 
• Movement difficulty 

Mode of administration

• Usually it is administered by intravenous infusions through a vein by an expert or a certified nurse
• Before infusion certain medications are prescribed to lessen the side effects.the drugs include paracetamol,chlorpheniramine,steroids
• The infusions are administered for about 4-7 hours during 1st infusion ,if tolerated well without any risks ,side effects then the infusions are given faster 
• The dosage includes 375 mg/m² once weekly for 4 weeks or 1 g on day 1 & 15.

The infused arm shows increase proteinemia 

Additional care should be taken before advicing to pregnant ,breastfeeding women or someone trying for a baby should use contraceptives. An year wait is recommended after the use of rituximab therapies 

Interactions

The possible interactions are quite common with the attenuated,non-attenuated , COVID  vaccines

Some other drugs include amphotericin -B,denosumab,certolizumab,cisplatin,fingolimod etc

Hypertensive drugs may interact with rituximab

Key points

• There is potential risk of fatal infusion reactions within 24 hrs .should be discontinued and inform to doctor
• Reactivation of hepatitis -B
• Mucocutaneous reactions like pemphigus,SJS,bullosa
• Contraindicated in history of hypersensitivity cases 
• Informing about the rituximab intake before any surgeries or extraction to the respective physician 

Conclusion 

• In case of infections/allergies discontinue its use after informing & consulting  the doctor immediately 
• Even Though the use of rituximab is safe and effective in certain conditions as described above .There are still ongoing discussions on their usage in multidrug therapies /in combination therapy and amount of dosage administration. 
• B-cell is considered as the exceptional strategy for most cases which directly affects the podocytes and its effects to alternate the anti Cd-20 preparations.This is possible with the rituximab.