Tocilizumab

Rituximab is a chimeric monoclonal antibody against CD20. CD20 is the protein broadly articulated on all B-cells including pre-B cells and memory B-cells. However it is absent on plasma cells. The exact role of CD20 is unknown but its expected to involve in B- cell activation by maintaing calcum influx in the cell. Rituximab binds to the CD20 and forms a cap there by drawing proteins to that side. This caping marks it for killing by NK cells. Nk cells have 80% success rate of killing caped B cells as compared to 40% in normal cells. Depleting B cells in RA results in remission and long term effects. So, anti CD therapy is useful in controlling diseases mediated by the hyperactivated B-cells such as leukemias, lymphomas, tissue transplant rejection and autoimmune diseases.
Rituximab is recommended for the treatment of Ra as a second line therapy when MTXalone and TNF inhibiors fail to produce response. Mostly it is used in combination with MTX but if a patient is intolerant to MTX, it can be administered alone. The adverse effects include cardiac arrest, infusion site reactions, cytokine release syndrome, renal failure, immune toxicity and pulmonary toxicity. The risk of opportunistic infections and activation of tuberculosis is less pronounced with RTX as compared to TNF inhibitors but there is a higher risk of a rare but very serious and fatal infection of multifocal leukoencephalopathy.

Other Anti- CD 20 biologics are

Ocrelizumab humanized (90%-95% human) B cell-depleting agent.
Ofatumumab (HuMax-CD20) a fully human B cell-depleting agent.[47]
obinutuzumab




Rituximab 179
Rituximab (RTX), amonoclonal chimeric anti-CD20 antibody, recog- 180
nizes a determinant expressed on intramedullary pre-B- to B-memory- 181
stage lymphocytes. The first controlled trial on RA was published in 182
2004 [43]. Because B cells, the target of RTX, play pivotal roles in RA 183
pathogenesis [44], serum biomarkers of B cell activation, such as the 184
presence of RF, or anti-CCP antibodies and elevated IgG level,were iden- 185
tified as potential predictors of response to RTX. 186
Depleting the majority of circulating B-cells induces clinical remis- 187
sion which can last for many months before relapse [45]. Peripheral 188
blood B cell re-population after RTX treatment is similar to what is ob- 189
served after bonemarrow transplantation, and predominantly involves 190
a subset of naïve or antigenically inexperienced transitional B cells de- 191
rived from an immature population. 192
RTX is approved in the European Union and the USA for the treat- 193
ment of RA after inadequate response to at least one TNF-inhibitor. It 194
is currently prescribed as a second line treatment of active RA in associ- 195
ation withmethotrexate. However, in daily practice, RTX can be admin- 196
istered without methotrexate in patients with intolerance or previous 197
adverse event to this drug [46]. 198
The combination of RTX administered IV as two 1000 mg infusion 199
cycles separated by 15 days and methotrexate is highly effective at 200
reducing disease activity at 6 months in RA. However, 35% of patients 201
do not achieve a significant response and, among those who initially respond, relapse in the next 6–12 months often occurs [47]. Anewcycle
204 is initiated after disease activity recurs.
205 The GISEA registry-based study showed a good efficacy for RTXwith
206 amean reduction of DAS 28 at 52 weeks ofmore than 1.50 points, with
207 maintenance over two years. No significant differences were observed
208 for patients treated or not with MTX both for mean DAS 28 and HAQ
209 variation and achievement of disease remission [48].
210 Patients seronegative for rheumatoid factor and anti-cyclic
211 citrullinated protein have worse responses, suggesting that these pa-
212 tients have non-B-cell-mediated disease and require a different thera-
213 peutic approach [49,50]. Despite the fact that RTX does not deplete
214 fully matured plasma cells, repeated administration of the biologic
215 agent frequently induces a reduction of immunoglobulins, particularly
216 immunoglobulin G (IgG),whichmay carry an increased risk of infection.
217 Before commencement of RTX, hepatitis B serology and liver func-
218 tion tests should be routinely performed. Reactivation of occult hepatitis
219 B infection has been reported in patients with RA treated with RTX. On
220 the other hand specific safety profile of RTX indicates an apparent
221 absence of increased risk of reactivation of tuberculosis, a low risk of
222 opportunistic infections, but possibly a small increased risk of the very
223 rare but serious neurological infection progressive multifocal leukoen-
224 cephalopathy, the risk ofwhichmay be higher in patientswith previous
225 immunosuppression.