Thus, for every patient on every visit day, ACR 20, 50 and 70 responses were assessed independently, resulting in different numbers for ACR responses at each given time point. Patients who discontinued during the LTE were requested to return for follow-up radiography at their next annual visit, regardless of subsequent prescribed treatment. Radiographs were taken at the time of discontinuation in those patients who declined to return for an annual visit and their next annual assessment imputed with linear extrapolation based on the last available annual visit and assessment at discontinuation.
Of the and patients randomised to abatacept and placebo, respectively, Baseline demographics and clinical characteristics of patients entering the LTE were comparable between treatment groups, as previously reported. All patients received concomitant MTX during the study. During the 3-year cumulative period mean abatacept exposure was The type and incidence of the most commonly reported AEs during the cumulative period were similar to those reported in the double-blind period, 1 2 as were the IRs of serious AEs SAEs.
Cardiac disorders were reported in 68 patients Summary of adverse events and malignancy type for all patients who received one dose of abatacept during 3 years of the study. IRs of infections and serious infections were lower in the cumulative versus the double-blind period table 1. Two cases of tuberculosis were documented in the cumulative period, both in the abatacept group; both patients discontinued.
One case was suspected in a year-old woman in the double-blind period. The patient did not experience any symptoms and no bacterial evidence of tuberculosis was found. During the LTE, tuberculosis was diagnosed presumptively in a year-old woman. The patient exhibited a response to tuberculosis therapy, although bronchial lavage and biopsy did not identify tuberculosis. During the cumulative period, malignant neoplasms were reported in 24 patients 1. The three cases of lung cancer were reported during the LTE in patients initially randomised to abatacept; all had a history of smoking.
Of the two cases of lymphoma, one was reported during the double-blind period malignant thyroid tumour of moderate intensity. The second case non-Hodgkin's lymphoma was reported during the first year of the LTE in a patient randomised to placebo.
During the cumulative period, 35 autoimmune AEs were reported. For patients originally randomised to abatacept, the proportions of ACR 20, 50 and 70 responders were maintained from year 1 to year 3 figure 1A. Clinical efficacy and patient-reported outcomes in abatacept-treated patients. At year 1, , , , , , , , , and patients were included in the PCS, MCS, physical function, role—physical, bodily pain, general health, vitality, social functioning, role—emotional and mental health assessments, respectively.
At year 3, , , , , , , , , and patients were included in the aforementioned assessments, respectively. A change of 3. The proportion of patients achieving low disease activity state or DASdefined remission in the original abatacept-treated group increased over 3 years figure 1B. Mean changes from baseline are shown in figure 1C.
Mean improvements from baseline in the physical component summary PCS and mental component summary MCS at year 1 were maintained over 3 years figure 1D. Of the SF subscales, the greatest improvement was observed in bodily pain and role—physical from baseline to years 1 and 3 figure 1D.
Mean changes from baseline in Genant-modified Sharp scores were progressively reduced from baseline to years 1, 2 and 3 figure 2A—C. Progression slowed even further between years 2 and 3, with a mean change in TS of 0. Impact on radiographic disease progression over 3 years of abatacept treatment. A Mean change from baseline in Genant-modified Sharp total score. B Mean change in erosion score. C Mean change in joint space narrowing score. D Cumulative probability plot showing change from baseline in total score.
Error bars represent the SEM. Cumulative probability plots of the distribution of change in TS over 3 years, at yearly intervals, show an improvement in radiographic progression with abatacept over time figure 2D. The proportion of patients with no radiographic progression increased during each year of abatacept treatment. Retention rates in long-term clinical trials provide an indication of the likelihood of patients continuing treatment over the long term in clinical practice.
The yearly discontinuation rate decreased during year 3, indicating the likelihood of patients to remain on treatment over the long term. Additionally, no unique or unexpected safety signals were detected with long-term exposure. Although it is considered inappropriate to make cross-trial comparisons of IRs, it may be noted that IRs of AEs and SAEs in this trial were within the lower range of IRs reported for other biologic therapies such as TNF inhibitors in similar patient populations.
This is consistent with previously reported IRs of malignancy in another trial of abatacept in established disease 11 and in comparator RA cohorts treated with conventional DMARDs 0. The use of mismatched donors in which disparity is only in the host versus graft direction because of recipient homozygosity is discouraged because of the potentially heightened risk for graft rejection.
Centers may perform extended typing e. DQB1 and DPB1 according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
Assent, when appropriate, will be obtained according to institutional guidelines. Must have a high risk hematologic malignancy as defined below: Acute myeloid leukemia AML.
Early T-Cell Precursor ETP phenotype In 2nd complete remission with B-lineage disease after a marrow relapse occurring less than 36 months from diagnosis. In a 2nd complete remission with T-lineage disease after an extra-medullary relapse occurring less than 18 months from diagnosis. In 3rd or greater complete remission after a marrow or extramedullary relapse d Patients with acute undifferentiated, biphenotypic, or bilineal leukemia, which is in 1st or greater complete remission CR or partial remission PR.
The patient is enrolled on a COG trial that utilizes unrelated donor HSCT and requires that patients be transplanted using an approach specified by the protocol that is in conflict with the approach specified in this protocol. Availability of a willing and suitable HLA identical related donor. Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
HIV infection. Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression. Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded. Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded.
Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers will not be excluded. Incompletely treated active tuberculosis Infection. Pregnancy positive serum b-HCG or breastfeeding.
Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials.
More Information. National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Graft vs Host Disease Malignancy. Drug: Abatacept Drug: placebo. Phase 2. Study Type :. Interventional Clinical Trial. Actual Enrollment :.
Triple Participant, Care Provider, Investigator. Study Start Date :. Actual Primary Completion Date :. Estimated Study Completion Date :. Drug: Abatacept Arm B-investigational prophylaxis with abatacept, a calcineurin inhibitor and methotrexate Other Name: Orencia. Washington, District of Columbia, United States, Methods: patients entered an open-label extension of the AIM Abatacept in Inadequate responders to Methotrexate trial and received abatacept.
Radiographic assessment of the hands and feet was performed at baseline, year 1 and year 2. At year 2, each patient's radiographs were scored for progression blinded to sequence and treatment allocation.
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