Rituximab (RTX) is anti-CD20 chimeric antibody that selectively targets B cells. CD20 is a molecule that functions as an antigen for it. CD20 is expressed on mature antibody producing B cells, ngunit hindi sa plasma cell.(1) Ang FDA ay inaprubahan ang paggamit ng Rituximab para sa paggamot ng B cell lymphomas.(2) Dahil ang pathogenic at clinical manifestations ng PV ay lilitaw upang antibody may kaugnayan, maaaring ito ay hypothesized na-alis ang mga antibody ng pathogenic at ng mga cell na gumawa ito, might be more effective than general nonspecific immune suppression. This is the rationale for using Rituximab in treating pemphigus vulgaris. Indeed, Ang tagumpay sa ang Rituximab ay sinusunod sa maraming mga autoimmune sakit na kung saan ay mediated sa pamamagitan ng mga antibodies tulad ng systemic lupus erythematosus at immune thrombocytopenic purpura.(3)
Sa isang kamakailan-lamang na pagsusuri ng mga magagamit na-publish na literatura sa wikang Ingles sa Rituximab ay tapos na. (4) There were 17 patients presented in ten different studies. These patients had been treated with RTX using the lymphoma protocol. In this protocol, patients are given four weekly infusions. The dose is 375 mg/m2 for each infusion. The results were variable, ngunit ang kabuuang ito ay lumitaw na 88% ng mga pasyente ay libre ng lesions, for at least a six months follow-up period. Unfortunately, marami ng mga pasyente ay itinuturing sabay-sabay sa maginoo immunosuppressive therapy (Puntod na bato). In many of them, the use of RTX allowed for lowering the dose of Prednisone. One of the major problems associated with RTX in these patients was infection. Four patients had serious infections and in addition one patient died from it. None of these patients got intravenous immunoglobulin (IVIg).
Dahil ang pinagsama-samang panitikan ay suportado ang paggamit ng RTX sa paggawa ng isang positibong klinikal na kahihinatnan, we decided to study the use of RTX in recalcitrant pemphigus vulgaris. Our major concerns were (ako) maaari ang paggamit ng RTX alisin maginoo immunosuppressive therapy, at (ii) could RTX therapy produce prolonged and sustained clinical remissions. Recently we have published data on 11 mga pasyente sa sa Oktubre 26, 2006 isyu ng New England Journal ng Medisina.(5) To the readers of the Quarterly, it would be important to identify the group of patients we studied by providing some key characteristics. The important features of this group were that they all had been treated initially with Prednisone and other immunosuppressive agents. The mean daily dose of Prednisone was 125 mg. All had been treated with mycophenolate morfetil, 10 sa azathioprine, 9 sa methotrexate at 6 with cyclophosphamide.
Dahil ang mga pasyente ay hindi tumugon sa maginoo immunosuppressive therapy, they were subsequently treated with IVIg. The IVIg was not totally effective. To augment the effect of IVIg, Dapsone with methotrexate was added to the IVIg. The mean duration of all previous systemic therapy, bago ang paggamit ng Rituximab, ay 68.8 buwan, nagpapahiwatig na ang sakit ay naroroon para sa 6 – 7 years and had not responded to all of the known therapies for PV. These patients also had extensive disease involving the skin and multiple mucous membranes. The patients were treated with RTX in a newly designed protocol never published before or used to treat any other disease. The patients were given the same dose of RTX as in previous studies (375 mg/m2). The protocol was as follows:
Bago ang pagsisimula ng RTX, the patient’s got one cycle of IVIg. Then during the first month of therapy, para sa unang tatlong linggo, they received weekly infusions of RTX. In the fourth week, they received one cycle of IVIg. This same procedure was repeated in the second month. Ang 3rd, 4ika, 5ika, at 6 na buwan, the patients received only one infusion of RTX followed by one cycle of IVIg. Hence, ang mga pasyente ay nakuha ng isang kabuuang 10 mga infusions ng RTX in sa partikular na protocol na ito.
Ilang sandali matapos ang pagsisimula ng RTX, the patient’s B cell counts were reduced to zero. Hence, the IVIg was given primarily to assist preventing infection. In addition, it was also used as an immunomodulatory agent. It was hypothesized that if the pathogenic antibody and the cells producing it were no longer present, ito ay magbigay ng immune system ng isang pagkakataon upang mangasiwa mismo sa estado predisease.
Katunayan ang lahat ng mga 11 patients have stayed in remission. The mean duration of remission has been 31.1 months. Two patients had recurrences. In both patients, ang mga recurrences ay itinuturing na may lamang RTX at ang mga pasyente ay nagpunta sa isang prolonged clinical pagpapatawad.
It is critical to be aware of the fact that RTX warrants the very rigorous prescreening procedure. Prior to initiation of RTX therapy, we have always obtained clearance from the primary care physician of the patient. In addition, oncologist isang ay sinusuri ang mga pasyente na nangangailangan ng isang CT scan ng ang leeg, dibdib, abdomen and pelvis to exclude any existing lymphomas. Evaluation of liver and kidney functions and the serological tests for various infections was done. During the RTX therapy, CBC sa, chemistries, ngunit pinaka-mahalaga, paligid dugo T & B cells were monitored on a very regular basis. Until the B cells have returned to normal, monthly infusions of IVIg were given. Once the B cells returned to normal, IVIg protocol ay nakumpleto na ang mga pasyente ng mga infusions sa 6, 8, 10, 12, 14, at 16 linggo pagitan.(6) We believed this was essential to help restore the immune system to its normal balance. Recurrences have not been seen to date in all of those patients in whom this protocol was completed. Hence the ability to complete the IVIg protocol is an integral component of this therapy and needs to be emphasized when initiating the therapy.
Kaya, ang pag-aaral ng isang limitadong bilang ng mga pasyente ay malinaw na sinabi na RTX ginamit sa sa IVIgaccording sa protocol na ito, according to this protocol, produces long-term clinical remission. None of the patients had any serious side effects and none of them developed any infections. Therefore, there is optimism to indicate that RTX would be a valuable form of therapy in treating patients who have recurrent disease who are non-responsive to conventional immunosuppressive therapy and only partially responsive or non-responsive to IVIg therapy. This protocol is certainly not the only protocol that could be effective. Indeed studies in the future might provide valuable information on the use of RTX using different protocols.
In closing it is important to emphasize two issues to the readership. First, that RTX is not for every PV patient. Second, RTX is not a benign harmless drug. Its use can have serious consequences. Experience with the drug is limited and additional studies that must include long- term follow-up are critical. If you think you are an appropriate candidate for RTX, mangyaring makipag-usap sa iyong dermatologo.
Dr. Ahmed ay maaaring maabot sa firstname.lastname@example.org </div>
Mga sanggunian1. Maloney DG, Smith B, Rose A. Rituximab: mechanism of action and resistance. Semin Oncol 2002;29(Suppl 2):2-9.
2. Rastetter W, Molina A, White CA. Rituximab: expanding role in therapy for lymphomas and autoimmune diseases. Annul Rev. Sa. 2004;55:477-503.
3. Chambers SA, Isenberg D. Anti-B cell therapy (Rituximab) in the treatment of autoimmune diseases. Lupus 2005;14:210-4.
4. Abdul Kader El Tal, MD, Marshall R. Posner, MD, Zachary Spigelman, MD, at A. Razzaque Ahmed, MD. Rituximab: A monoclonal antibody to CD 20 used in the treatment of pemphigus vulgaris. JAAD September 2006;55(3):449-466.
5. Ang isang. Razzaque Ahmed, M.D., Zachary Spigelman, M.D., Lisa A. Cavacini, Ph.D., at Marshall R. Posner, M.D. Treatment of Pemphigus Vulgaris with Rituximab and Intravenous Immune Globulin. N Engl J Med. 2006;355:1772-9
6. Ang isang. Razzaque Ahmed, MD, DSC; Mark V. Dahl, MD; for the Consensus Development Group. Consensus Statement on the Use of Intravenous Immunoglobulin Therapy in the Treatment of Autoimmune Mucocutaneous Blistering Diseases. Arch Dermatol. 2003, Agosto;139:1051-1059.