Rituximab

(BAN, USAN, rINN)
Synonyms: IDEC-102; IDEC-C2B8; Rituksimab; Rituksimabi; Rituximabum. Immunoglobulin G1 (human-mouse monoclonal IDEC-C2B8 chain anti-human antigen CD 20), disulfide with human-mouse monoclonal IDEC-C2B8
Cyrillic synonym: Ритуксимаб.

💊 Chemical information

CAS — 174722-31-7.
ATC — L01XC02.
ATC Vet — QL01XC02.

💊 Adverse Effects, Treatment, and Precautions

Infusion of rituximab has been associated with a cytokine release syndrome of fever, chills, and rigors, usually within 2 hours of beginning therapy (see also below). Other reported symptoms include pruritus, urticaria, rashes, dyspnoea, bronchospasm, angioedema, transient hypotension, and flushing. Asthenia, headache, rhinitis, myalgia, dizziness, and hypertension may also be associated with infusion reactions. Severe cases may be associated with tumour lysis syndrome, acute renal failure, respiratory failure, and death. Hypersensitivity reactions manifest similarly to the cytokine release syndrome, but usually occur within minutes of starting infusion. Mucocutaneous reactions, some fatal, and including Stevens-Johnson syndrome or toxic epidermal necrolysis have also occurred. Patients with an extensive tumour burden, pulmonary tumour infiltration or pulmonary insufficiency may be at increased risk of severe reactions and should be treated with caution and possibly a decreased initial infusion rate. Therapy should be interrupted in patients who develop severe symptoms and only resumed, at half the previous rate, once all signs and symptoms have resolved. Premedication with analgesics, antihistamines, and possibly corticosteroids is recommended in all patients before receiving rituximab. Reactivation of hepatitis B virus (HBV) has occurred in some patients; fulminant hepatitis, hepatic failure, and fatalities have been reported. Patients at high risk of HBV infection should be screened before starting rituximab therapy and carriers should be monitored for signs of active infection or hepatitis during and for several months after therapy. Rituximab should be stopped if viral hepatitis develops. Other serious infections, which may be fatal, can occur with rituximab. Cases of progressive multifocal leukoencephalopathy, some fatal, have been reported with rituximab. Haematological adverse effects including lymphopenia, leucopenia, neutropenia, thrombocytopenia, and anaemia have occurred in some patients; effects are considered mild and reversible. Complete blood and platelet counts should be monitored regularly. Exacerbation of heart failure and angina pectoris has also been reported, and other cardiac events include arrhythmias and tachycardia. Gastrointestinal disturbances may also occur. Abdominal pain, bowel obstruction, and perforation, in some cases fatal, have been reported with rituximab combination chemotherapy.
1. Mohrbacher A. B cell non-Hodgkin’s lymphoma: rituximab safety experience. Arthritis Res Ther 2005; 7 (suppl 3): S19–S25
2. Kimby E. Tolerability and safety of rituximab (MabThera). Cancer Treat Rev 2005; 31: 456–73.

Effects on the blood.

Late-onset neutropenia (defined as neutropenia occurring 30 days after the last dose) has been reported in patients receiving rituximab.1
1. Rios-Fernández R, et al. Late-onset neutropenia following rituximab treatment in patients with autoimmune diseases. Br J Dermatol 2007; 157: 1271–3.

Effects on the eyes.

About 20 minutes after the start of a rituximab infusion, a patient developed bilateral conjunctivitis without pain, lachrymation, or discharge. No other clinical manifestations of a hypersensitivity reaction were apparent, and the conjunctivitis resolved spontaneously, about 30 minutes after the end of the infusion. No recurrence was evident with subsequent rituximab therapy.1
1. Marinella MA. Bilateral conjunctivitis due to rituximab. Ann Pharmacother 2007; 41: 1318.

Effects on the gast

rointestinal tract. In November 2006 the manufacturer noted that 47 cases of bowel obstruction (9 fatal) and 37 cases of gastrointestinal perforation (4 fatal) had been reported in patients given rituximab.1 Interpretation of data was difficult due to confounding factors; however, a contributory role of rituximab could not be excluded. The mean time to onset of symptoms was 6 days (range 1 to 77 days) for documented perforation. Complaints of abdominal pain, especially early in a course of rituximab treatment, should prompt thorough diagnostic evaluation and treatment.
1. Roche, Canada. Reports of bowel obstruction and gastrointestinal perforation with RITUXAN (rituximab) (issued 10th November 2006). Available at: http://www.hc-sc.gc.ca/dhp-mps/ medeff/advisories-avis/prof/_2006/rituxan_3_hpc-cps-eng.php (accessed 30/07/08)

Effects on the lungs.

Pulmonary reactions have been reported with rituximab use,1 including reversible interstitial pneumonia2-4 and interstitial fibrosis.5 A fatal intra-alveolar haemorrhage in 1 patient was attributed to a hypersensitivity reaction to rituximab.6
1. Wagner SA, et al. Rituximab-induced interstitial lung disease. Am J Hematol 2007; 82: 916–19
2. Burton C, et al. Interstitial pneumonitis related to rituximab therapy. N Engl J Med 2003; 348: 2690–1
3. Jullien V, et al. Une pneumopathie alvéolo-interstitielle hypoxémiante associée à la prise de rituximab. Rev Mal Respir 2004; 21: 407–10
4. Swords R, et al. Interstitial pneumonitis following rituximab therapy for immune thrombocytopenic purpura (ITP). Am J Hematol 2004; 77: 103–4
5. Leon RJ, et al. Rituximab-induced acute pulmonary fibrosis. Mayo Clin Proc 2004; 79: 949, 953
6. Alexandrescu DT, et al. Fatal intra-alveolar hemorrhage after rituximab in a patient with non-Hodgkin lymphoma. Leuk Lymphoma 2004; 45: 2321–5.

Effects on the nervous system.

As of December 2006, the FDA had received a total of 24 reports of progressive multifocal leukoencephalopathy (PML) in patients given rituximab.1 PML is a fatal demyelinating disease that follows reactivation of latent JC or PK polyomavirus (also known as papovavirus) in the CNS; the virus is present in about 80% of adults. In the first 12 cases reported to the FDA, 10 patients tested positive for the JC virus and 1 had confirmed BK virus.
1. FDA. Rituximab (marketed as Rituxan): progressive multifocal leukoencephalopathy (PML). FDA Drug Safety Newsletter 2007; 1: 3–5. Available at: http://www.fda.gov/cder/dsn/ 2007_fall/2007_fall.pdf (accessed 07/02/08)

Infusion-related reactions.

By November 1998 there had been 74 cases of serious infusion-related reactions to rituximab reported worldwide, with 8 fatal cases.1 An estimated 12 000 to 14 000 patients had been treated. The reaction usually occurs within the first 2 hours of infusion and the underlying mechanism is believed to be a severe cytokine release syndrome, with some elements of tumour lysis syndrome.1-3 In one series of cases tumour necrosis factor-α and interleukin-6 levels were found to peak 90 minutes after the onset of the infusion, and these elevated cytokine levels coincided with infusion-related symptoms.2 The reaction is usually most marked after the first infusion and subsequent infusions are usually tolerated, emphasising that this is not a true hypersensitivity reaction.4 Patients with a high tumour burden (lesions over 10 cm in diameter or more than 500 000 circulating malignant cells/mm3), a history of pulmonary infiltration or insufficiency, or underlying cardiac disease are believed to be at greater risk of severe reactions.1,2,4 The UK CSM recommends that premedication with an analgesic and an antihistamine should always be given before rituximab, and corticosteroids should be considered.1 However, serious or fatal reactions have occurred despite such premedication.3,4 Alternative infusion schedules and/or combination therapy with chemotherapeutic drugs may be required to decrease the tumour burden before rituximab therapy.2,4
1. Committee on Safety of Medicines/Medicines Control Agency. Rituximab (MabThera): serious infusion-related adverse reactions. Current Problems 1999; 25: 2–3. Also available at: http:// www.mhra.gov.uk/home/idcplg?IdcService=GET_ FILE&dDocName=CON2023233&RevisionSelectionMethod= LatestReleased (accessed 26/04/06
2. Winkler U, et al. Cytokine-release syndrome in patients with Bcell chronic lymphocytic leukaemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999; 94: 2217–24
3. Lim L-C, et al. Fatal cytokine release syndrome with chimeric anti-CD20 monoclonal antibody rituximab in a 71-year-old patient with chronic lymphocytic leukaemia. J Clin Oncol 1999; 17: 1962–3
4. Byrd JC, et al. Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance. J Clin Oncol 1999; 17: 791–5.

Pregnancy.

Giving 4 cycles of rituximab (with doxorubicin, vincristine, and prednisolone) to a pregnant woman with lymphoma, from 21 weeks of gestation until delivery at 35 weeks, resulted in no adverse effects to either the mother or the infant.1In another report, a 31-year-old woman was diagnosed with nonHodgkin’s lymphoma during pregnancy. She received 6 cycles of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Two months after treatment, she spontaneously delivered a premature but healthy infant. Patient and child were clinically assessed every 3 months; the infant’s B cells were severely diminished at birth but recovered over 6 to 12 weeks. Rituximab concentrations in both mother and child also decreased as expected. No adverse effects were seen during 16 months of follow-up.2 In 2 case reports of rituximab use during the first trimester of pregnancy, no significant adverse effects on the neonates were seen; transient granulocytopenia and lymphopenia were reported.3,4 A 35-year-old woman diagnosed with Burkitt’s lymphoma in week 15 of pregnancy received 4 weekly infusions of rituximab starting in week 16, followed by four courses of rituximab with CHOP, and then 2 courses of CHOP alone. In week 41, a healthy infant was delivered by caesarean section. Both the mother and child had very high serum concentrations of rituximab at birth with a complete absence of B cells; rituximab levels in the cord blood serum were three times that in the mother’s serum. However, B-cell recovery was reported to be rapid, and no overt infectious complications were seen in the child up to the age of 26 months; growth and developmental status were also normal.5 Nonetheless, licensed product information advises against rituximab use during pregnancy, given the potential for B-cell depletion in the fetus; women of child-bearing potential should use effective contraceptive methods during treatment and for up to 12 months after therapy.
1. Herold M, et al. Efficacy and safety of a combined rituximab chemotherapy during pregnancy. J Clin Oncol 2001; 19: 3439
2. Decker M, et al. Rituximab plus CHOP for treatment of diffuse large B-cell lymphoma during second trimester of pregnancy. Lancet Oncol 2006; 7: 693–4. Correction. ibid.; 706
3. Kimby E, et al. Safety of rituximab therapy during the first trimester of pregnancy: a case history. Eur J Haematol 2004; 72: 292–5
4. Ojeda-Uribe M, et al. Administration of rituximab during the first trimester of pregnancy without consequences for the newborn. J Perinatol 2006; 26: 252–5
5. Friedrichs B, et al. The effects of rituximab treatment during pregnancy on a neonate. Haematologica 2006; 91: 1426–7.

💊 Pharmacokinetics

The mean maximum plasma concentration of rituximab has been reported to increase with successive infusions; however, considerable interindividual variation is seen. Serum concentrations are negatively correlated with tumour burden and the number of circulating B-cells. The mean terminal half-life is about 20 days. Rituximab is bound to B lymphocytes, and is detectable in the body for 3 to 6 months after treatment.

💊 Uses and Administration

Rituximab is a chimeric monoclonal antibody to CD20 antigen used in the treatment of non-Hodgkin’s lymphomas. It is used as monotherapy in relapsed or refractory low-grade or follicular lymphoma, or as first-line treatment with combination chemotherapy, such as CVP (cyclophosphamide, vincristine, and prednisolone). Rituximab monotherapy may also be used in patients with low-grade stable disease after first-line treatment with CVP chemotherapy. It is also indicated for maintenance therapy in patients with refractory or relapsed follicular lymphoma who respond to induction chemotherapy that may or may not have contained rituximab. Rituximab is also used with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) or other anthracycline-based regimens for CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma. Rituximab also forms part of the combination regimen employing ibritumomab tiuxetan. Rituximab with methotrexate is used in adults with moderate to severely active rheumatoid arthritis who have had an inadequate response to DMARDs, including tumour necrosis factor inhibitors. Rituximab is given by intravenous infusion, diluted in sodium chloride 0.9% or glucose 5% to a final concentration of between 1 and 4 mg/mL. The first infusion is given initially at a rate of 50 mg/hour; subsequently this may be increased in increments of 50 mg/hour every 30 minutes to a maximum of 400 mg/hour, if well tolerated. Subsequent doses may be begun at a rate of 100 mg/hour, and increased in increments of 100 mg/hour every 30 minutes to a maximum of 400 mg/hour. In the UK for the treatment of refractory or relapsed follicular lymphoma, rituximab is given as a single agent in a usual dose of 375 mg/m 2 once weekly for 4 doses; in the USA 8 doses may be given. Patients in either country may be re-treated after relapse for a further 4 doses. When given with combination chemotherapy such as CVP (for follicular lymphoma) or CHOP (for diffuse large B-cell lymphoma), rituximab 375 mg/m 2 is given on day 1 of the chemotherapy cycle, after the corticosteroid component of the regimen, for a total of 8 cycles. In patients previously treated with 6 to 8 cycles of CVP chemotherapy and who have not progressed, rituximab 375 mg/m 2 may be given once weekly for 4 doses, repeated every 6 months, for up to 16 doses. For maintenance treatment in those who have responded to induction chemotherapy, rituximab 375 mg/m 2 is given once every 3 months until disease progression or for a maximum period of 2 years. In the regimen with ibritumomab tiuxetan, rituximab is usually given at a dose of 250 mg/m 2 . In the treatment of rheumatoid arthritis, rituximab is given in a dose of 1 g, for 2 doses; the infusions are separated by 2 weeks. It is given with methotrexate, and corticosteroids are recommended before each infusion to reduce the incidence and severity of infusion reactions. Rituximab is also under investigation for the treatment of a number of other conditions including chronic lymphocytic leukaemia, multiple sclerosis, ANCAassociated vasculitis, and SLE, including lupus nephritis.

Administration.

Rituximab has been used intralesionally in the treatment of cutaneous B-cell lymphoma. There are reports of benefit, with long-term remission in some patients,1 but rapid recurrence in others.2 In a study of 8 patients, intralesional rituximab was given to 6 patients, in doses of 10 to 30 mg per lesion, 3 times weekly; if clinical remission was incomplete, another cycle of 3 injections was given 1 month later. Two patients were treated intravenously with weekly infusions for 4 weeks. Complete remission was seen in all 8 patients. No relapse was seen in those given intravenous therapy, but recurrences were seen in 4 of the 6 patients treated intralesionally. Moderate pain was reported during intralesional injection.3
1. Paul T, et al. Intralesional rituximab for cutaneous B-cell lymphoma. Br J Dermatol 2001; 144: 1239–43
2. Roguedas AM, et al. Intralesional therapy with anti-CD20 monoclonal antibody rituximab: local and systemic efficacy in primary cutaneous B-cell lymphoma. Br J Dermatol 2005; 152: 541–4
3. Kerl K, et al. Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases. Br J Dermatol 2006; 155: 1197–1200.

Administration in children.

Although not licensed in the UK or the USA for use in children, there are reports of benefit in children with various diseases, such as auto-immune haemolytic anaemia, idiopathic thrombocytopenic purpura (see also below), and post-transplantation lymphoproliferative disease,1 as well as rheumatoid arthritis, and SLE.2 Standard doses of 375 mg/m2weekly have usually been given, in most cases for a median course of 4 doses.
1. Giulino LB, et al. Treatment with rituximab in benign and malignant hematologic disorders in children. J Pediatr 2007; 150: 338–44
2. El-Hallak M, et al. Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. J Pediatr 2007; 150: 376–82.

Eye disorders.

Orbital pseudolymphomas are uncommon benign tumours which usually affect the lachrymal gland, orbital soft tissue, or extra-ocular muscles. Clinical presentation includes painless onset of ptosis, proptosis, diplopia, or eyelid swelling. There are reports of durable response to rituximab.1
1. Witzig TE, et al. Treatment of benign orbital pseudolymphomas with the monoclonal anti-CD20 antibody rituximab. Mayo Clin Proc 2007; 82: 692–9.

Glomerular kidney disease.

In a report of 5 patients with corticosteroid-resistant nephrotic syndrome, 4 patients had a complete remission and 1 patient had a partial remission after treatment with rituximab in standard doses for 4 weeks. Complete remission was maintained in 3 patients, despite tapering of corticosteroids and calcineurin inhibitors.1
1. Bagga A, et al. Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 2007; 356: 2751–2.

Haemolytic anaemia.

Rituximab has been used in the treatment of severe refractory auto-immune haemolytic anaemia of various causes, including warm,1,2 cold,3-5 and mixed6,7 disease.
1. Quartier P, et al. Treatment of childhood autoimmune haemolytic anaemia with rituximab. Lancet 2001; 358: 1511–13
2. Gottardo NG, et al. Successful induction and maintenance of long-term remission in a child with chronic relapsing autoimmune hemolytic anemia using rituximab. Pediatr Hematol Oncol 2003; 20: 557–61
3. Sparling TG, et al. Remission of cold hemagglutinin disease induced by rituximab therapy. Can Med Assoc J 2001; 164: 1405
4. Engelhardt M, et al. Severe cold hemagglutinin disease (CHD) successfully treated with rituximab. Blood 2002; 100: 1922–3
5. Berentsen S, et al. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood 2004; 103: 2925–8
6. Morselli M, et al. Mixed warm and cold autoimmune hemolytic anemia: complete recovery after 2 courses of rituximab treatment. Blood 2002; 99: 3478–9
7. Webster D, et al. Prompt response to rituximab of severe hemolytic anemia with both cold and warm autoantibodies. Am J Hematol 2004; 75: 258–9.

Haemorrhagic disorders.

Although data are limited, reports suggest that rituximab may be an effective alternative for the treatment of acquired haemophilia after established therapies have failed.1,2
1. Maillard H, et al. Rituximab in postpartum-related acquired hemophilia. Am J Med 2006; 119: 86–8
2. Stachnik JM. Rituximab in the treatment of acquired hemophilia. Ann Pharmacother 2006; 40: 1151–7.

Idiopathic thrombocytopenic purpura.

Rituximab has been reported1-3 to be effective in patients, including children and infants, with idiopathic thrombocytopenic purpura refractory to standard treatments. However, a review4 cautioned against the indiscriminate use of rituximab in this patient population, given the lack of controlled data.
1. Zaja F, et al. The B-cell compartment as the selective target for the treatment of immune thrombocytopenias. Haematologica 2003; 88: 538–46
2. Bengtson KL, et al. Successful use of anti-CD20 (rituximab) in severe, life-threatening childhood immune thrombocytopenic purpura. J Pediatr 2003; 143: 670–3
3. Wang J, et al. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr 2005; 146: 217–21
4. Arnold DM, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 2007; 146: 25–33.

Malignant neoplasms.

Reviews.
1. NICE. Rituximab for aggressive non-Hodgkin’s lymphoma (issued September 2003). Available at: http://www.nice.org.uk/ nicemedia/pdf/65_rituximab_nonhodgkins_fullguidance.pdf (accessed 30/07/08
2. Avivi I, et al. Clinical use of rituximab in haematological malignancies. Br J Cancer 2003; 89: 1389–94
3. Cvetković RS, Perry CM. Rituximab: a review of its use in nonHodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 2006; 66: 791–820
4. Held G, et al. Rituximab for the treatment of diffuse large B-cell lymphomas. Expert Rev Anticancer Ther 2006; 6: 1175–86
5. van Oers MH. Rituximab maintenance in indolent lymphoma: indications and controversies. Curr Oncol Rep 2007; 9: 378–83
6. Schulz H, et al. Chemotherapy plus rituximab versus chemotherapy alone for B-cell non-Hodgkin’s lymphoma. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2007 (accessed 24/07/08)
7. Molina A. A decade of rituximab: improving survival outcomes in non-Hodgkin’s lymphoma. Annu Rev Med 2008; 59: 237–50.

Pemphigus.

Rituximab has been reported to be of benefit in pemphigus vulgaris and 17 cases have been reviewed.1It was used in patients with severe and widespread disease that had not responded to usual therapy with corticosteroids and immunosuppressants. A dose of 375 mg/m2 once weekly was used and most patients were given a course of 4 doses. Most patients showed some improvement from rituximab, including 9 who were free of clinical disease for more than 6 months and 5 who had a partial response. However, although concomitant therapy could be reduced in 8 patients, only 2 were able to stop systemic corticosteroids and immunosuppressants; in 6 cases this information was not reported. Rituximab might therefore be useful for remission induction when corticosteroids have not been effective, but long-term follow-up is needed. Rituximab with normal immunoglobulins has also been reported to be effective in patients with refractory pemphigus vulgaris.2 Rituximab has been reported to be of benefit in pemphigus foliaceus,3,4 a less common variant of pemphigus. A single cycle of 4 weekly infusions of rituximab was reported to achieve complete remission in 12 of 14 patients with pemphigus vulgaris and 6 of 7 patients with pemphigus foliaceus; 2 patients in the former group achieved delayed complete remission. Of these 20 patients, 6 with pemphigus vulgaris and 3 with pemphigus foliaceus had a relapse; 2 of these 9 patients were given a second course of rituximab and again achieved complete remission. After 34 months of follow-up, 18 patients were free of disease, and 8 of these were not receiving any systemic therapy.5
1. El Tal AK, et al. Rituximab: a monoclonal antibody to CD20 used in the treatment of pemphigus vulgaris. J Am Acad Dermatol 2006; 55: 449–59
2. Ahmed AR, et al. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med 2006; 355: 1772–9
3. Goebeler M, et al. Rapid response of treatment-resistant pemphigus foliaceus to the anti-CD20 antibody rituximab. Br J Dermatol 2003; 149: 899–901
4. Arin MJ, et al. Anti-CD20 monoclonal antibody (rituximab) in the treatment of pemphigus. Br J Dermatol 2005; 153: 620–5
5. Joly P, et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med 2007; 357: 545–52.

Rheumatoid arthritis.

Rituximab is of benefit in patients with rheumatoid arthritis refractory to standard therapy.1-3 The ability of rituximab to prevent articular damage, its efficacy for extra-articular manifestations, the efficacy and safety of repeated courses, and long-term effects on the immune system remain to be determined.4 Radiographic data from a placebo-controlled study showed a trend towards less progression of structural joint damage with a course of rituximab (2 doses); assessment was made at 24 weeks.5 In a consensus statement, European and Canadian rheumatologists stated that re-treatment with rituximab may be considered after week 24 in those who respond to initial therapy.6 In the UK, NICE states that rituximab with methotrexate is a treatment option for adults with severe active rheumatoid arthritis who have had an inadequate response to DMARDs or are intolerant of them; previous therapy should have included at least one tumour necrosis factor α inhibitor. Treatment with rituximab and methotrexate should continue only if patients show an adequate response, and repeat courses should be given no more often than every 6 months; specialist supervision is advised.7
1. Edwards JCW, et al. Efficacy of B-cell—targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004; 350: 2572–81
2. Summers KM, Kockler DR. Rituximab treatment of refractory rheumatoid arthritis. Ann Pharmacother 2005; 39: 2091–5
3. Higashida J, et al. Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-
α treatment.
J Rheumatol 2005; 32: 2109–15
4. Looney RJ. B cell-targeted therapy for rheumatoid arthritis: an update on the evidence. Drugs 2006; 66: 625–39
5. Cohen SB, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthritis Rheum 2006; 54: 2793–2806
6. Smolen JS, et al. Working Group on the Rituximab Consensus Statement. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 2007; 66: 143–50
7. NICE. Rituximab for the treatment of rheumatoid arthritis: Technology Appraisal 126 (issued August 2007). Available at: http:// www.nice.org.uk/nicemedia/pdf/word/TA126guidance.doc (accessed 13/05/08)

Scleroderma.

Rituximab is under investigation for the management of scleroderma.

Skin disorders.

In addition to reports of efficacy in pemphigus (see above), rituximab has been reported to be of benefit in refractory cases of pemphigoid1 and epidermolysis bullosa acquisita.2,3
1. Schmidt E, et al. Rituximab in autoimmune bullous diseases: mixed responses and adverse effects. Br J Dermatol 2007; 156: 352–6
2. Crichlow SM, et al. A successful therapeutic trial of rituximab in the treatment of a patient with recalcitrant, high-titre epidermolysis bullosa acquisita. Br J Dermatol 2007; 156: 194–6
3. Sadler E, et al. Treatment-resistant classical epidermolysis bullosa acquisita responding to rituximab. Br J Dermatol 2007; 157: 417–19.

Systemic lupus erythematosus.

Rituximab is under investigation for the treatment of SLE.1
1. Sfikakis PP, et al. Rituximab anti-B-cell therapy in systemic lupus erythematosus: pointing to the future. Curr Opin Rheumatol 2005; 17: 550–7.

Thrombotic microangiopathies.

Rituximab has been reported1-3 to be of benefit in relapsed or refractory thrombotic thrombocytopenic purpura.
1. Zheng X, et al. Remission of chronic thrombotic thrombocytopenic purpura after treatment with cyclophosphamide and rituximab. Ann Intern Med 2003; 138: 105–8
2. Reddy PS, et al. Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura. Ann Hematol 2005; 84: 232–5
3. Kosugi S, et al. Rituximab provided long-term remission in a patient with refractory relapsing thrombotic thrombocytopenic purpura. Int J Hematol 2005; 81: 433–6.

💊 Preparations

Proprietary Preparations

Arg.: MabThera; Austral.: MabThera; Austria: MabThera; Belg.: MabThera; Braz.: MabThera; Canad.: Rituxan; Chile: MabThera; Cz.: MabThera; Denm.: MabThera; Fin.: MabThera; Fr.: MabThera; Ger.: MabThera; Gr.: MabThera; Hong Kong: MabThera; Hung.: MabThera; Indon.: MabThera; Irl.: MabThera; Israel: MabThera; Ital.: MabThera; Jpn: Rituxan; Malaysia: MabThera; Mex.: MabThera; Neth.: MabThera; Norw.: MabThera; NZ: MabThera; Philipp.: MabThera; Pol.: MabThera; Port.: MabThera; Rus.: MabThera (МабТера); S.Afr.: MabThera; Singapore: MabThera; Spain: MabThera; Swed.: MabThera; Switz.: MabThera; Thai.: MabThera; Turk.: MabThera; UK: MabThera; USA: Rituxan; Venez.: MabThera.
Published February 07, 2019.