Protherae et al.
Early case reports of remission of coexisting RA in patients with non-Hodgkin’s lymphoma (NHL) who were given rituximab provided encouraging results that this agent might lead to clinical improvement in patients with active RA. The case report described a 53-year-old man with NHL who subsequently developed arthropathy. He was treated with 700 mg of chimeric monoclonal anti-CD20 antibody for four weeks. An initial improvement of symptoms was noted at the third week of treatment. During the following weeks, symptoms resolved completely.
Felson et al.
Several small, open-label trials and one double-blind, randomized, controlled trial were conducted to evaluate the efficacy and safety of rituximab for patients with refractory RA. All of the trials used the American College of Rheumatology’s (ACR’s) definition of criteria for improvement. The target percentage for improvement of individual criteria has traditionally been set at 20% (ACR 20). An ACR 20 response is defined as an improvement of at least 20% from baseline in counts of both tender and swollen joints, as well as three of the remaining disease-activity measures of the ACR core set: (1) the physician’s assessment of disease activity, (2) the patient’s assessment of physical function, and (3) the value for one acute-phase reactant. Targets of improvement of 50% and 70% (ACR 50 and 70 responses, respectively), however, have increasingly been used in clinical trials. canadian pharmacy cialis
Edwards and Cambridge
The first indication of the therapeutic potential of rituximab in RA was provided in a small, open-label study of five patients who had not responded to treatment consisting of at least five DMARDs. Patients received a combination of ritux-imab (300 mg on day 2 and 600 mg on days 8, 15, and 22), cyclophosphamide (750 mg on days 4 and 17), and oral prednisolone (30-60 mg/day for 22 days). All patients achieved an ACR 50 response, and three patients received an ACR 70 response at six months. None of the patients experienced major adverse drug events (ADEs).
Leandro et al.
Another pilot study reported outcomes achieved in 22 patients with RA that was considered refractory to standard DMARDs. The results supported earlier data on the effectiveness of different treatment regimens in which dosages of rituximab, cyclophosphamide, and corticosteroids were varied.
Cohort I. Five patients received rituximab as four intravenous (IV) infusions. On day 2, the patients were given 300 mg; on days 8, 15, and 22, they received 600 mg. They also received cyclophos-phamide 750 mg as an IV infusion on days 4 and 17 and oral prednisolone 60 mg on days 1 to 23.
Cohort II. Four patients received either one or two 300-mg/m2 doses of rituximab 14 days apart without cyclo-phosphamide.
Cohort III. Ten patients received two 300- to 350-mg/m2 doses of rituximab and, in most cases, two doses of cyclo-phosphamide 750 mg.
Cohort IV. Six patients were given the same protocol as those in Cohort I but without a prednisolone cover.
Cohort V. Four patients received 500 mg/m2 of rituximab, with two 750-mg doses under variable prednisolone cover (Table 1).
Of the 20 patients in this study who achieved an ACR 20 response by six months, only 19 had received both ritux-imab and cyclophosphamide therapy. As with the other pilot studies, no major ADEs were reported; only two infusion-related reactions were observed.
Table 1 Interventions and Efficacy Outcomes in Patients with Rheumatoid Arthritis Who Were Treated with Rituximab
Rituximab Dosage (by IV Infusion)
|300 mg then 3 x 600 mg (2 x 600 mg in one patient)||Prednisolone for three to six weeks and cyclophosphamide, 2 x 750 mg||ACR 70 in three of five patientsACR 50 in two of five patients at 26 weeks
ACR 70 in three of five patients at 18 months
|300-700 mg/m2||Prednisolone 605 or 640 mg (in two patients only)||ACR 20 in one patient only at six months|
|600 or 700 mg/m2||Cyclophosphamide1,000-1,500 mg
(2,250 mg in one patient)
|ACR 70 in six of 10 patientsACR 50 in two of 10 patients at six months|
|2 x 600 mg||Cyclophosphamide, 2 x 750 mg (2 x 600 mg in two patients)||ACR 70 in two of six patients ACR 50 in two of six patients ACR 20 in two of six patients at six months|
|500 mg/m2||Cyclophosphamide,2 x 750 mg||Short-duration benefit only; all patients experienced relapse at six months.|
DeVita et al.
Another trial investigated the use of rituximab without cyclophosphamide for patients with RA refractory to DMARDs and biological agents. Five women with RA who fulfilled the ACR criteria gave informed consent to treatment with rituximab. Therapy consisted of four weekly IV infusions of 375 mg/m2. Only low-dose steroids, NSAIDs, or antimalarial drugs could be continued during the trial. Only two patients demonstrated a response of at least ACR 50 by 10 months; however, reductions in C-reactive protein and serum rheumatoid factor levels were observed in four patients. No significant ADEs were noted.
Moore et al.
A phase 2 trial examined the efficacy and safety of rituximab in patients who had not successfully responded to hematopoietic stem cell transplantation (HSCT) as a therapy for RA.Ten patients were enrolled in this trial. All of them received rituximab 1 g, two weeks apart, with no major adverse sequelae. They were observed for 12 months. Eligible patients received cyclophosphamide 100 to 200 mg/kg as part of their transplantation protocol, and all were able to continue with DMARDs and steroid therapy for at least the first two months of the trial. A total of eight out of 10 patients experienced major clinical responses, achieving a 50% to 70% improvement in disease parameters.