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D Stablein

Publications and source records attributed to D Stablein.

At least 19 recordsLinked to original sources
PubMed2006

Decreased risk of renal allograft thrombosis associated with interleukin-2 receptor antagonists: a report of the NAPRTCS.

Graft thrombosis is the most common cause of first year graft failure in pediatric renal transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database was analyzed for cases of graft failure due to thrombosis among patients transplanted from 1998 to 2004. The impact of interleukin-2 (IL-2) receptor antagonists as induction therapy was determined. There were a total of 51 graft failures due to thrombosis among the 2750 reported renal transplants (1.85%) (95% CI (1.39%, 2.41%)). This represents the most common cause of graft loss during the first year post-transplant accounting for 35% of first year losses and 18% of all graft losses. The incidence of thrombosis among patients who received IL-2 receptor antibodies was 1.07% (12/1126) compared to 2.40% (39/1624) among patients who did not (OR 0.44, 95% CI 0.23, 0.84, p = 0.014). Use of IL-2 receptor blockade was the only significant prognostic factor in a multivariate model with previously identified risk factors. Analysis of NAPRTCS data found that the use of IL-2 receptor antibodies as induction therapy is associated with a significantly decreased risk of graft failure due to thrombosis. This provocative finding requires further investigation to determine whether thrombotic failure can be decreased by this therapeutic strategy.

Adolescent↗
PubMed2001

Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus Type 1 vaccine with or without gp120: a phase 2 study in higher- and lower-risk volunteers.

Live attenuated viral vectors that express human immunodeficiency virus (HIV) antigens are being developed as potential vaccines to prevent HIV infection. The first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55, and protease) was conducted in 435 volunteers with and without gp120 boosting, to expand the safety database and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection. Neutralizing antibodies to the MN strain were stimulated in 94% of volunteers given vCP205 plus gp120 and in 56% of volunteers given vCP205 alone. CD8(+) cytotoxic T lymphocyte cells developed at some time point in 33% of volunteers given vCP205, with or without gp120. Phase 3 field trials with these or similar vaccines are needed, to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study.

AIDS Vaccines↗
PubMed2000

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗
PubMed2000

Improved graft survival after renal transplantation in the United States, 1988 to 1996.

BACKGROUND: The introduction of cyclosporine has resulted in improvement in the short-term outcome of renal transplantation, but its effect on the long-term survival of kidney transplants is not known. METHODS: We analyzed the influence of demographic characteristics (age, sex, and race), transplant-related variables (living or cadaveric donor, panel-reactive antibody titer, extent of HLA matching, and cold-ischemia time), and post-transplantation variables (presence or absence of acute rejection, delayed graft function, and therapy with mycophenolate mofetil and tacrolimus) on graft survival for all 93,934 renal transplantations performed in the United States between 1988 and 1996. A regression analysis adjusted for these variables was used to estimate the risk of graft failure within the first year and more than one year after transplantation. RESULTS: From 1988 to 1996, the one-year survival rate for grafts from living donors increased from 88.8 to 93.9 percent, and the rate for cadaveric grafts increased from 75.7 to 87.7 percent. The half-life for grafts from living donors increased steadily from 12.7 to 21.6 years, and that for cadaveric grafts increased from 7.9 to 13.8 years. After censoring of data for patients who died with functioning grafts, the half-life for grafts from living donors increased from 16.9 years to 35.9 years, and that for cadaveric grafts increased from 11.0 years to 19.5 years. The average yearly reduction in the relative hazard of graft failure after one year was 4.2 percent for all recipients (P<0.001), 0.4 percent for those who had acute rejection (P=0.57), and 6.3 percent for those who did not have acute rejection (P<0.001). CONCLUSIONS: Since 1988, there has been a substantial increase in short-term and long-term survival of kidney grafts from both living and cadaveric donors.

Adult↗
PubMed1999

Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil--a prospective randomized study. Steroid Withdrawal Study Group.

BACKGROUND: Prospective randomized trials have shown a reduced rate of acute rejection (AR) in mycophenolate mofetil-treated kidney transplant recipients. We hypothesized that this increased protection from AR could allow successful prednisone (P) withdrawal in cyclosporine/mycophenolate mofetil/P-treated recipients. METHODS: A multicenter, prospective, randomized, double-blind trial of P withdrawal at 3 months post-transplant was initiated. Entry criteria were: primary transplant, adult, no AR by 90 days, mycophenolate mofetil dose > or =2 g/day, cyclosporine dose = 5-15 mg/kg/ day, P dose = 10-15 mg/day. Study participants were randomized to have P tapered over 8 weeks (beginning at 3 months posttransplant) to 0 vs. 10 mg/day. Prestudy power analysis determined 500 recipients should be randomized for 80% statistical power to test equivalence of the primary endpoint, AR, or treatment failure at 1 year posttransplant. By design, the study was to be stopped if interim data precluded reaching equivalence. An established data safety monitoring board monitored the study. RESULTS: After 266 patients were enrolled, the patient enrollment was stopped (after safety monitoring board review) because of excess rejection in the P withdrawal group. The Kaplan-Meier estimate of the cumulative incidence of rejection or treatment failure within 1 year posttransplant (+/-95% confidence interval) for the maintenance group was 9.8% (4.4%; treatment failure, 14.9%); for the withdrawal group, 30.8% (21.0%; 39.3%). Treatment differences in the distribution of time to event were highly significant (P = 0.0007). Of note, risk was higher in blacks (39.6%) versus nonblacks (16.0%) (P<0.001). At 1 year post-transplant, there was no difference between groups in patient or graft survival. For the patients with functioning grafts at 6 months posttransplant, withdrawal patients had lower cholesterol (P = 0.0005), had higher creatinine (P = 0.03), and were less likely to use antihypertensives (P = 0.001). These differences persist to 1 yr posttransplant. CONCLUSIONS: We conclude that for recipients on cyclosporine/mycophenolate mofetil/P with no AR at 90 days, the chance of developing subsequent AR is small; if P is tapered and withdrawn, the risk increases (but the majority remain free of acute and chronic rejection). After withdrawal, the risk of AR is different for blacks versus nonblacks. Withdrawal patients had a lower cholesterol level and less need for antihypertensives.

Adolescent↗
PubMed1999

Safety of kidney biopsy in pediatric transplantation: a report of the Controlled Clinical Trials in Pediatric Transplantation Trial of Induction Therapy Study Group.

BACKGROUND: Historically, young children undergoing renal transplantation have lower allograft survival than adults, and potential causes of this are being addressed by the North American Pediatric Renal Transplant Cooperative Study through the National Institutes of Health-sponsored study Cooperative Clinical Trials in Pediatric Transplantation. Included in this study is evaluation of surveillance renal biopsies (SB) and clinically indicated biopsies (CB). Few data exist in children to identify the risk involved with renal transplant biopsies. METHODS: Questionnaires were mailed to 21 participating centers asking for descriptions of adverse events associated with kidney biopsies, with choices limited to none, gross hematuria, perinephric hematoma, and other. Further clinical details were obtained from review of medical records of all patients with reported adverse events. Data were collected from 19 centers on 126 patients. RESULTS: Eighty-six patients had undergone 212 biopsies (75 SB and 137 CB). Nine biopsy-related adverse events were reported (4.2%): three SB (4.0%) and six CB (4.4%). Gross hematuria was reported in six patients (2.8%): two SB (2.7%) and four CB (2.9%). A perinephric hematoma was reported in one patient. Two patients with intraperitoneal kidneys developed significant bleeding after biopsy and required transfusions and surgical exploration. No patient lost kidney function or required nephrectomy after biopsy. No difference was noted in adverse events between SB at day 5 or 12 versus CB. CONCLUSION: Evaluation of transplanted kidney tissue may provide important information for the care of the transplantation patient. This analysis suggests that transplanted kidney biopsies can be performed with minimal risks in pediatric patients.

Adolescent↗
PubMed1999

Trends in immunosuppressive therapy: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) data registry has now compiled data for 11 years, and includes data on 6038 renal transplants in 5516 patients. With the availability of new data and immunosuppressive medications, trends in their usage continue to change. NAPRTCS data have previously demonstrated that increased doses of cyclosporin A (CsA) are associated with improved allograft outcomes, and there has been a steady increase in the dose of CsA given post-transplantation. Transplants that occurred in 1987, 1989, 1991, and 1993 received a mean one-year post-transplant dose of 6.5, 7.0, 7.7, and 8.2 mg/kg/d, respectively. In the 1995 cohort, the dose decreased to 7.4 mg/kg/d. Since the introduction of Neoral, its use has steadily increased. Of the 1997 cohort, 81% report Neoral as the formulation of CsA used. The dose of CsA given, however, has not changed. At day 30 post-transplant, the dose was 7.0 mg/kg/d for Sandimmune and 7.4 mg/kg/d for Neoral. Finally, the outcome in black transplant patients is inferior to that of nonblack. Evaluation of CsA blood levels revealed that at 1 year post-transplant, black patients consistently have CsA levels higher than nonblacks, and a lower percentage of black patients have a CsA level < 100 ng/mL. The percentage of patients using triple therapy (prednisone, azathioprine, and CsA) remained stable from 1987 to 1993 at 80-85%. However, in 1996 only 30% of patients were receiving triple therapy. This is probably due to the introduction of mycophenolate mofetil (MMF). Comparing the 1996-97 cohorts, there has been no significant change in the percentage of patients receiving prednisone (96.2% vs. 95.4%) or CsA (83.1% vs. 79.6%). However, during this time, the use of azathioprine has decreased from 50.0% to 35.8%, the use of tacrolimus has increased from 2.5% to 10.8%, and the use of MMF has increased from 6.5% to 35.8%.

Adolescent↗
PubMed1998

Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen. AIDS Vaccine Evaluation Group.

Effective human immunodeficiency virus (HIV) vaccination may require induction of neutralizing antibodies (NAs) and CD8+ cytotoxic T lymphocytes (CTL) to prevent transmission and control early infection. Recombinant envelope proteins induce NAs but rarely CD8+ CTL responses, and vaccinia vectors containing HIV-1 envelope elicit CD8+ cytotoxicity but few NAs. To benefit from both approaches, 56 vaccinia-naive subjects were randomized to a regimen of priming with recombinant vaccinia gp160LAI and boosting with recombinant gp120SF-2, gp120LAI, gp120MN, or gp160MN. Of 51 persons for whom assays were done, 26 demonstrated envelope-specific CTL. Boosting with gp120, compared with gp160, elicited significantly more NAs and CD4-blocking antibodies. Neutralization of the homologous and heterologous HIV-1 laboratory strains occurred in all subjects receiving vac/env and gp120 and was detectable in 91% of the subjects for >6 months. Thus, vaccine regimens in which one component elicits primarily CTL and the other NAs offer promise for the development of an effective HIV-1 vaccine strategy.

AIDS Vaccines↗
PubMed1998

Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group.

A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1MN gp160 or 10(5.5) TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or 2 months and ALVAC-gp160 or 50 microg of HIV-1SF2 recombinant (r) gp120 in microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6, and 12 months. All vaccines were well-tolerated. Neither vaccinia-immune status before vaccination nor ALVAC dose affected HIV immune responses. HIV-1MN and HIV-1SF2 neutralizing antibodies were detected more often (100%) in ALVAC-gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%) alone. ALVAC-gp160/rgp120 also elicited more frequent HIV V3-specific and fusion-inhibition antibodies, antibody-dependent cellular cytotoxicity, lymphoproliferation, and cytotoxic CD8+ T cell activity than did either vaccine alone. Trials with ALVAC expressing additional HIV components and rgp120 are underway.

AIDS Vaccines↗
PubMed1998

Renal transplantation in children with congenital nephrotic syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

The database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) was examined to identify factors that contribute to the poor transplant outcome rate seen in patients with Congenital Nephrotic Syndrome (CNS) (1). Between January 1, 1987 and January, 1997, 132 transplant recipients with the primary diagnosis of CNS were registered. Analysis of the index renal transplants for 78 living donor transplants (LDTx) and 54 cadaver transplants (CADTx) revealed a graft failure rate of 20.5% and 50.0%, respectively. A proportional hazards regression analysis of the CNS patients indicated that cadaver donor source (relative risk increase of 3.9, p<0.001) and recipient age less than 2 years of age (relative risk increase of 2.6, p=0.002) were simultaneous significant predictors of poor graft survival. Patients with CNS demonstrated decreased graft survival compared to the remainder of the registry adjusted for age and donor source (p=0.04). Graft failures were attributed to vascular thrombosis (26%), patient death with functioning graft (23%), chronic rejection (21%) and acute rejection (19%). Graft failure attributed to thrombosis occurred more frequently in CNS patients than in patients with other primary diseases (8.3% vs. 2.9%, p=0.002). Graft failure due to patient death with a functioning graft also occurred more frequently in CNS patients than in patients with other primary diseases (7.5% vs. 2.6%, p<0.003). Infections were the causes of death in 50% (5 of 10) of CNS patients with a functioning graft. Infection as a cause of death with functioning grafts was significantly greater in CNS patients (3.8%) than the rest of the registry (0.8%, p<0.006). We conclude that there is a high rate of renal graft failure in pediatric patients with CNS. Vascular thrombosis and death with a functioning graft were more frequent in patients with CNS compared to patients with other primary diseases. Care should be taken to eliminate risk factors for hypercoagulability and infections prior to transplantation in children with CNS.

Adolescent↗
PubMed1997

Risk factors for vascular thrombosis in pediatric renal transplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study.

Vascular thrombosis remains a major cause of graft failure, accounting for 12.2% of failed index transplants and 19.2% of repeat transplants. We conducted a special study to identify the risk factors for vascular thrombosis. A total of 4394 transplants (2060 living donor [LD] transplants and 2334 cadaver donor [CAD] source transplants) were evaluated. The respective vascular thrombosis rates for LD and CAD transplants were 38/2060 (1.8%) and 100/2334 (4.2%) (P<0.001). Univariate analysis showed that the rate of graft loss due to thrombosis was significantly higher in younger children (less than 2 years of age) as compared with older age groups (2-5 years, 6-12 years, and more than 12 years of age) (9.0% vs. 5.5%, 4.4%, and 3.5% for CAD transplant recipients and 3.5% vs. 3.4%, 0.7%, and 1.9% for LD graft recipients). Recipients of kidneys from cadaver donors less than 5 years of age had a significantly higher thrombosis rate (8.3%) than did recipients from older donor groups (5-10 years, 4.5%; greater than 10 years, 3.2%). Recipients of kidneys with cold ischemia time greater than 24 hr also had a higher thrombosis rate (5.6%), as compared with recipients of kidneys with a shorter cold ischemia time (3.2%). Recipients of antilymphocyte therapy on day 0 or day 1 were at dimished risk of graft loss due to thrombosis (2.2% vs. 4.1%, P=0.001). Comparable trends were seen for both LD and CAD organ recipients. LD organ recipients with a history of prior transplantation had a significantly higher rate of thrombosis as compared with those who received a primary transplant (4.6% vs. 1.6%, P=0.005). For both LD and CAD organ recipients, the occurrence of acute tubular necrosis was a significnat risk factor for the development of thrombosis. Regression analysis showed that for LD organ recipients, a history of prior transplantation increased the risk for thrombosis, whereas increasing recipient age had a linear decreasing risk effect. The use of antilymphocyte antibody or cyclosporine on day 0/1 decreased the risk for thrombosis. For CAD kidney recipients, organ cold ischemia time greater than 24 hr increased the risk for thrombosis. The use of antibody induction therapy, donors greater than 5 years of age, and increasing recipient age were factors that decreased the risk for thrombosis.

Age Factors↗
PubMed1997

A partially grouped logrank test.

We propose a modified version of the standard logrank test for survival data in which the first contribution to the statistic is based on grouping of data before a pre-selected grouping time. The grouping is accomplished by artificially constructing the first table based on the product limit estimates of the proportions surviving at the grouping time. Remaining contributions to the statistic are identical to that of the standard logrank statistic. The approach has the advantage of being uninfluenced by non-proportional hazards differences prior to the grouping time while being almost as efficient as the usual logrank test for proportional-hazards alternatives. The statistic is particularly useful for interim monitoring in situations where early difference between treatments are unimportant and/or lagged treatment effects are anticipated. We report simulation studies to verify and investigate the test's properties.

Bone Marrow Transplantation↗
PubMed1997

Renal transplantation in children from 1987-1996: the 1996 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The 1996 Annual Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes data voluntarily collected from 130 centers on 4329 children and adolescent patients who received renal transplants on or after January 1, 1987. This report updates information on transplants; data on dialysis and chronic renal insufficiency have, for the first time, been reported separately (in submission). The NAPRTCS registry shows that the majority of pediatric renal transplants are performed in children above 6 years of age (73%). The most frequent diagnoses include obstructive uropathy (16%), aplastic/hypoplastic/dysplastic kidneys (16%), and focal segmental glomerulosclerosis (12%). Pre-emptive transplantation was performed in 24% of patients. Triple drug maintenance therapy with prednisone, cyclosporine and azathioprine was used by >70% of all transplant recipients throughout 7 years of follow-up. Fifty-six per cent of transplant recipients were rehospitalized during months 1-5 (51% live donor (LD), 62% cadaver donor (CD)), with rejection and infection as the main causes. In the period 30-35 months post-transplant, 19-22% of patients (163 LD, 185 CD) were rehospitalized. The median time to the first rejection was 46 days for CD transplants and 377 days for LD grafts (p<.001). Six-year graft survival rates were 73% and 56% for LD grafts and CD grafts, respectively (p<.001). The overall growth deficit was constant over a period of 60 months. However, children transplanted under 5 years of age reduce their height deficit by about one-third compared to an increase in height deficit of up to 22% for older children. The NAPRTCS data analysis also demonstrates a delay in first rejection episodes in LD compared to CD transplants, and a steady improvement in CD graft survival over the past 5 years in pediatric transplant recipients.

Adolescent↗
PubMed1996

Clinical correlates of chronic rejection in pediatric renal transplantation. A report of the North American Pediatric Renal Transplant Cooperative Study.

A total of 1699 patients with living donor transplants and 1795 patients with cadaver donor transplants entered between January 1987 and November 1994 in the North American Pediatric Renal Transplant Cooperative Study registry form the cohort for this report. Failure from chronic rejection occurred in 76 (4.5%) of living donor transplants and 149 (8.3%) of cadaver transplants. Chronic rejection is the leading cause of graft failure, with 27% of living donor and 26.7% of cadaver donor graft failures attributed to chronic rejection. Univariate and multivariate analyses of various risk factors revealed acute rejection (relative risk [RR]=3.1, P<0.001) and greater than two acute rejections (RR=4.3, P<0.001)to be the most common correlates of chronic rejection. Additionally, late initial acute rejection (>365 days; RR=2.3, P<0.001) was also correlated. Cadaver donor source (RR=1.6, P=0.001) and African-American race (RR=1.6, P<0.003) were weaker but significant risk factors. An analysis of cyclosporine dosing revealed tht a dose of <5mg/kg/day at day 30 was also a risk factor (RR=1.5, P=0.027). Our study concludes that acute rejection is the single most critical element in the genesis of chronic rejection. Thus, measures to prevent the first episode of acute rejection could ameliorate the incidence of chronic rejection.

Adolescent↗
PubMed1996

Combination treatment of rheumatoid arthritis using azathioprine and methotrexate: a 48 week controlled clinical trial.

To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA), a double blind, prospective, multicenter, controlled trial was carried out. Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5/50-7.5/100) with opportunity to increase dosage at 6 week intervals. Patients were evaluated for clinical and laboratory improvement and assessed for radiologic progression at 48 weeks. One hundred ten patients remained on the initial, randomly assigned therapy. Response was defined as 30% or greater improvement in at least 3 of 4 variables, and occurred in the following: 38% on the combination arm, 26% on AZA, and 45% on MTX (p = 0.06). A trend for decreased radiologic progression was seen in the MTX group. Adverse experiences and treatment termination occurred more frequently in the combination and AZA arms relative to the MTX group. The most frequent causes for treatment discontinuations were lack of effectiveness, gastrointestinal adverse effects and liver enzyme elevation. This study establishes that the combination of MTX and AZA in the dosages employed is not associated with more toxicity than treatment with single agents, but enhanced efficacy is not seen. A trend toward decreased radiographic progression was noted in the MTX treated patients.

Antirheumatic Agents↗
PubMed1995

Analysis of rejection outcomes and implications--a report of the North American Pediatric Renal Transplant Cooperative Study.

For this study, we analyzed the role of rejection in graft failure in children. Rejection results were examined after 3004 pediatric renal transplants (1367 living donor, 1637 cadaver source). A total of 3453 (1298 living donor, 2155 cadaver source) rejection episodes have occurred, for rejection ratios of .95 for living donor and 1.32 for cadaver source transplants, with a constant difference of 18% points after four months, in the percentage of patients ever experiencing a rejection. Rejection results were examined by patient age (0-1 vs. 2-5 vs. 6-12 vs. > or = 13). Rejection ratios, annualized rejection frequency, time to first rejection, and mean number of rejections for patients with rejection were not elevated in the younger patients. However, for the initial rejection episode, recipients less than six years of age had significantly (P < .001) poorer outcome from the rejection episode with an increased risk of graft failure in both donor source groups. This age effect on rejection outcome is only seen with the first rejection episode and is not observed with subsequent rejection episodes.

Adolescent↗
PubMed1995

Comparison of azathioprine, methotrexate, and the combination of the two in the treatment of rheumatoid arthritis. A forty-eight-week controlled clinical trial with radiologic outcome assessment.

OBJECTIVE: To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA) in a double-blind, prospective, multicenter, controlled trial. METHODS: Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5mg MTX/week plus 50 mg AZA/day-7.5 mg MTX/week plus 100 mg AZA/day), with opportunity to increase the dosage at 6-week intervals. The patients were evaluated for significant clinical and laboratory improvement and assessed for radiologic progression at 48 weeks. RESULTS: One hundred ten patients remained on the initial, randomly assigned therapeutic regimen. The percentage of patients who were responders, defined as those who had 30% or greater improvement in at least 3 of 4 variables, was 38% for the combination treatment, 26% for AZA, and 45% for MTX (P = 0.06). A trend toward decreased radiologic progression was seen in the MTX-treated patients. Termination of treatment due to adverse experience occurred more frequently with combination and AZA treatments than with MTX treatment. Lack of effectiveness, adverse gastrointestinal effects, and liver enzyme elevation were the most frequent causes of treatment discontinuation. CONCLUSION: This study establishes that the combination of MTX and AZA in the dosages utilized is not associated with more toxicity than treatment with single agents; however, enhanced efficacy is also not seen. There is a trend toward decreased radiologic progression in patients treated with MTX.

Antirheumatic Agents↗