Home Page - About the Arthritis Center -Hopkins Rheumatology - Myositis Center - Vasculitis Center - Scleroderma Center
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| Jon Giles, M.D. and Joan Bathon, M.D.
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Abstract 527: Safety and Efficacy of a Human Monoclonal Antibody to IL-15 (AMG 714) in Patients with Rheumatoid Arthritis: Results from a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial IL-15, an inflammatory cytokine with pleotropic effects, plays a role in sustaining inflammation in RA. A previous phase I study of AMG 714, a fully human monoclonal antibody directed against IL-15, demonstrated human safety and tolerability of a dose of 4mg/kg/week. Here, McInnes et al present efficacy and safety data of AMG 714 from an interim analysis of an ongoing phase II/III trial. Methods: RA patients nave to therapy with biologics and and active disease despite treatment with at least one conventional DMARD were randomized to receive placebo or one of four doses of AMG 714: 40, 80, 160, or 280 mg injected subcutaneously every 2 weeks. All patients received two loading doses of AMG 714 or placebo loading doses, according to treatment allocation. Stable background methotrexate, NSAIDs, and low dose corticosteroids were continued. Patients were treated for twelve weeks, with clinical assessments every two weeks for the first sixteen weeks. The primary efficacy outcome was ACR20 response at 12 weeks. Results: 110 patients with completed data collection for 14 weeks comprised the population for this interim analysis. Twenty-one to 23 patients were enrolled in each of the 5 groups. Patient characteristics were typical for RA clinical trials (mean age around 50 years, approximately 75% women, predominantly Caucasian race, etc) and balanced between the study groups. Disease activity at entry was high, with mean DAS28 scores in the 6 to 7 range. Approximately two-thirds of patients were receiving background methotrexate at entry. At twelve weeks, patients receiving the 280 mg dose of AMG 714 had achieved an ACR 20 response statistically significantly different than patients in the placebo arm (62% vs. 26%, respectively). Numerical differences were noted in the patients receiving the other active treatment dosages compared to placebo, but these differences were not statistically significant. Statistical difference in efficacy between the 280 mg and placebo groups was not sustained to 14 weeks (largely due to patient withdrawal - which was higher in the placebo group than in the active treatment arms). Combining all patients receiving AMG 714, 62.8% of patients demonstrated at least a 20% reduction in CRP at week 14, compared to 38.9% in the placebo group. The proportions of patients reporting adverse events in the active treatment groups were similar to those in the placebo group. Injection site reactions were common, with 25% of patients reporting injection site reactions in the highest AMG 714 dosage group. Three serious adverse events occured requiring patient withdrawal from the study: one deep venous thrombosis, one sepsis secondary to a finger infection, and one elevation of LFTs. None of these events occurred in the highest AMG 714 dosage group. No deaths occurred within the study interval. No patients had developed antibodies against AMG 174 by week 24. Conclusions: AMG 174 at the 280 mg dose was well tolerated and demonstrated significant clinical efficacy over placebo by 12 weeks of therapy. Editorial Comments: These preliminary data are promising, but caution is advised in interpreting them due to the small numbers of patients studied thus far (less than 20 in the placebo group by the primary efficacy endpoint). IL-15 is an extremely attractive target given our current understanding of its multifaceted proinflammatory role in RA. Results from the completed study with a larger study population are eagerly awaited to see if these clinical responses remain as robust. | |||||||||||||||||||||||||||||||||||||
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Abstract 517: Results of a Phase II Study of Interleukin-1 (IL1)-Trap in Moderate to Severe Rheumatoid Arthritis Objective: IL-1, like TNF-a, is a proinflammatory molecule found in increased amounts in rheumatoid joints. IL-1 Trap is a recombinant high affinity inhibitor of IL-1 that is composed of both the Type I IL-1 receptor and the IL-1 receptor accessory protein, coupled to the Fc portion of IgG1. This was a 12-wk, multicenter, placebo-controlled phase II study to evaluate the safety and efficacy of IL1-Trap in patients with moderate to severe rheumatoid arthritis (RA). Methods: 201 subjects with moderate to severe RA, who had failed at least one DMARD, were randomized to receive weekly subcutaneous injections of placebo or IL-1 Trap 25, 50, or 100 mg. Patients were allowed to remain on pre-study doses of MTX, SSZ, HCQ, leflunomide, but treatement with other DMARDs or biologics was not permitted. The primary endpoint was the ACR20 response. Results: Baseline demographic and disease severity characteristics were similar among the 4 groups. Mean swollen joint count was 21.6, tender joint count 28.4, ESR 35.6, CRP 2.33 mg/dl, HAQ 1.5, and DAS28 5.61. The primary outcome (ACR20) was not different between placebo and any of the IL-1 trap groups. There were significant differences between 100 mg IL-1 trap and placebo for DAS28 and EULAR responses.
Levels of CRP, ESR, IL6, and SAA were dose-dependently decreased with IL1-Trap. No significant infectious complications were observed in the IL1-Trap groups. Injection site burning occurred in 34% of patients receiving placebo or 100 mg IL1-Trap (due to the diluent). Conclusion: IL-1 Trap was not more effective than placebo as measured by ACR20 response, although it did show modest efficacy using other disease activity parameters. IL1-Trap was well tolerated and showed dose-dependent reductions in biomarkers of the acute phase response. Editorial Comment The role of IL-1 in joint inflammation and destruction in RA remains unclear. Prior studies with a receptor antagonist of IL-1 (kineret; Anakinra) showeed only modest efficacy in RA but these results have been thought to be due to the relatively short half-life of kineret. IL-1 trap, in contrast, has much higher affinity and considerably longer half-life than kineret. Thus, if IL-1 does play a critical role in driving rheumatoid inflammation (as TNF does), then one would expect significant efficacy with the IL-1 trap molecule. Yet, these results are quite disappointing. It is possible, however, that doses higher than 100 mg might be efficacious since inflammatory biomarkers were responsive to dosing with IL-1 trap, and since there is a modest response in DAS28/EULAR responses with 100 mg of IL-1 trap. | |||||||||||||||||||||||||||||||||||||
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Abstract 518: Treatment Response to Methotrexate, Intraarticular Steroid and Cyclosporine/Placebo (CIMESTRA) in Early RA Objective: To investigate the efficacy of treatment with methotrexate (MTX), intraarticular betametasone, and cyclosporine (CYA) in patients with early RA. Methods: Patients with early RA of less than 6 months duration (n=160) were randomized to receive MTX 7.5 mg qwk + CYA 2.5 mg/kg (MTX+CYA) or MTX + placebo-CYA (MTX+PLA) for 12 months. At each visit (week 0, 2, 4, 6, 8, monthly thereafter) patients had steroid injections in all swollen joints (maximum of 4). Starting at week 8, the presence of persistent synovitis also required a stepwise increase in MTX to maximum of 20 mg/week, and stepwise increase of CYA (or CYA placebo) to maximum of 4 mg/kg. Clinical response was assessed by ACR20, 50 and 70 scores and ACR and DAS remission criteria. Analysis was by intention to treat. Results: Baseline demographic and disease activity measures were similar between the treatment groups. Median tender joint count was 14, swollen joint count 11, age 53, disease duration 14 weeks. 67% of participants were women, 65% seropositive, and 48% erosive. ACR responses and medication at 12 months are shown below.
The DAS scores declined from approximately 5.5 at baseline to 2.0 post-treatment in both groups (p NS). ACR remission rates, and percent achieving DAS scores < 3.1, were similar in the two groups (p NS). Serious adverse events occurred in two MTX+PLA patients (thrombocytopenia and severely elevated liver enzymes). After 12 months s-creatinine in MTX+CYA was 83 mmol/l (60-122), in MTX+PLA 79 mmol/l (57-118), p= 0.025. Blood pressure was well controlled (< 140/90) by adding antihypertensive treatment in 10 MTX+CYA and 4 MTX+PLA patients. Conclusion: The combination of MTX and intraarticular steroid achieved excellent disease control in early RA. The addition of CYA resulted in higher ACR20 (but not ACR50 or ACR70) response, and trends towards lower doses of concomitant i.a. steroids and MTX. The addition of CYA resulted in a minor, but statistically significant increase, in s-creatinine and was associated with need to institute anti-hypertensive treatment in a larger number of patients. Editorial Comment: The addition of cyclosporine to a treatment regiment of MTX + intraaraticular steroid injections had a marginal benefit at best, showing improvement in ACR20 but not ACR50 or 70 responses. Prior studies adding cyclosporine to MTX have had similarly weak or no effect. During her presentation in San Antonio, Dr. Hetland showed that both treatment groups achieved ACR20 responses very quickly. The rapidity of response was undoubtedly due to the intraarticular steroid injections. As shown in the Table above, although the mean (or median?) number of injections was 9-11, the maximum given was 49-51 over 12 months !!! It is hard to imagine that this would be a preferred route of treatment by most patients. Rather, if given a choice, one would imagine that oral prednisone would be preferable to this many injections. | |||||||||||||||||||||||||||||||||||||
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Abstract 519: A Randomized Placebo Controlled Trial with an Anti-MCP-1 (CCL2) Monoclonal Antibody in Patients with Rheumatoid Arthritis Objective: Monocyte chemoattractant protein-1 (MCP-1/CCL2), as the name implies, is a key chemoattractant for monocyte migration and therefore a potential therapeutic target for rheumatoid arthritis (RA). The objective of this study was to evaluate the efficacy of a fully human anti-MCP-1 monoclonal antibody (ABN912) for the treatment of RA. Methods: Patients with active RA despite methotrexate (MTX) treatment were enrolled in a 18 week double-blind, randomized, placebo controlled, sequential dose escalation (0.3, 1.0, 3.0 and 10.0 mg/kg) phase I/II study of ABN912, with an extension phase at the highest tolerated dose. Infusions were administered on day 1 and day 15. In the dose escalation phase, 4 cohorts of 8 patients each, randomized in a 3:1 ratio with placebo, underwent arthroscopic synovial tissue (ST) biopsy before and 7 weeks after treatment. Immunohistochemical analysis was used to characterize changes in CD3+ and CD22+ lymphocytes, CD68+ macrophages, and ST MCP-1. Results: 43 patients were enrolled, 32 in the escalation phase and 11 additional patients in the extension phase (10.0 mg/kg). Eleven patients were treated with placebo. All antibody doses were well tolerated. One serious adverse event (viral pneumonia) was suspected to be related to the study drug. Pharmacokinetic analysis showed a dose related increase in both ABN912-complexed total MCP-1 and free MCP-1. At the highest dose level, free MCP-1 was significantly higher than baseline and correlated with a significant increase in CRP in a majority of patients; in addition, a trend towards an increase in the number of ST CD68+ macrophages was observed. There was no apparent clinical response to treatment as measured by ACR responder criteria. Conclusion: The pharmacodynamics of ABN912 with the formation of ABN912/MCP-1 circulating complexes and elevations of free MCP-1 preclude the ability to assess MCP-1 as a target for therapeutic intervention in RA. Editorial Comment: Anti-MCP-1 therapy not only did not reduce the number of macrophages in RA synovia, it appeared to increase them and, moreover, increased CRP levels in treated patients. This effect was opposite of what was hypothesized, and is difficult to understand unless MCP-1 has some anti-inflammatory effects that were adversely antagonized. A critical question in approaching strategies to reduce synovial macrophages is what is the half-life of the resident synovial macrophage? If prolonged, then a strategy that limits influx of new monocytes, but does not affect the viability of established macrophages, may not have a measurable effect on numbers of synovial macrophages for many months. | |||||||||||||||||||||||||||||||||||||
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Abstract 520: Phase II Study of Interferon Beta 1afor the Treatment of Patients with Active Rheumatoid Arthritis Objective In a previous open label pilot trial, interferon (IFN) was demonstrated to have immuno-modulatory effects on synovial tissue and appeared to convey clinical benefit to patients with rheumatoid arthritis (RA). The objective of the current study was to assess the efficacy of IFN-bin combination with methotrexate (MTX) on clinical and radiological parameters in patients with early active RA. Methods: Two hundred nine (209) patients with active RA despite MTX treatment for at least 6 months were randomized to receive: placebo (0.05ml or 0.5 ml), 2.2 g (0.05 ml) or 44 g (0.5 ml) of IFN-badministered in subcutaneous injections three times weekly for 24 weeks. The primary outcome was a change in radiological scores at week 24. The secondary endpoint was the ACR20 responder index. Synovial biopsy specimens were obtained at baseline and following treatment from a subset of patients to evaluate for the presence of inflammatory cells. In addition, levels of collagen crosslinks in urine were measured at several time points. Results: There were no statistically significant differences with regard to changes in radiological scores or clinical parameters in the IFN-b- and placebo-treated groups. Furthermore, microscopic analysis of synovial tissue showed no significant change in the scores for infiltration by inflammatory cells after IFN-btreatment. And urinary levels of collagen crosslinks were unchanged between the treatment groups. Conclusion: At the doses tested, treatment with IFN-bthree times weekly given in combination with methotrexate did not induce any clinical or radiological benefit in RA patients. Editorial Comment: In contrast to IFN-gamma (IFN-a) which is proinflammatory, IFN-bhas a variety of anti-inflammatory effects. In collagen induced arthritis in mice, administration of IFN-bsuppresses joint swelling and bone erosions. In the current clinical trial in RA, the results are disappointingly negative and suggest that inflammatory pathways in human RA are not responsive to the inhibitory effects of IFN-bor that the proinflammatory stimuli are disproportionately overwhelming. Another possibility is that the doses of IFN- utilized are too low to see efficacy. Since the doses chosen are those used for treatment of multiple sclerosis, and higher doses are associated with significant toxicity, it is unlikely that an additional clinical trial at higher doses will be undertaken. | |||||||||||||||||||||||||||||||||||||
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Abstract 521: Therapeutic Response at Two Years in the TEMPO Trial in a Sub-group of Patients with Early Rheumatoid Arthritis (RA) Objective: The one-year results of the TEMPO trial demonstrated that the combination of etanercept and methotrexate (MTX) was significantly better in reducing disease activity, improving functional disability, and halting radiographic progression than MTX or etanercept monotherapy in patients with RA. Prior studies have suggested that early treatment of RA with highly effective treatments might result in better overall outcomes than delaying such treatment. Approximately 30% of the patients enrolled in TEMPO had a disease duration of less than 3 years; therefore, a post hoc analysis was conducted to evaluate the effect of therapy in this group of patients. Methods: 682 RA patients were treated with MTX, etanercept 25 mg twice weekly, or the combination of etanercept with MTX. The primary outcomes were ACR-N AUC at 6 months and change from baseline in Total Sharp Score (TSS) at 1 year. For this 2-year interim analysis, early RA was defined as disease duration of 3 years or less. Results: The response to combination treatment in the early RA group was significantly higher compared to methotrexate (Table 1). Likewise, patients with disease duration of 3 years or less had relative responses for ACR 20, 50, 70, HAQ, DAS, and DAS 28 similar to those of the overall population. DAS remission was achieved in 19%, 34%, and 43% of early RA patients treated with methotrexate, etanercept, and combination, respectively. Conclusions: After 2 years of treatment, a high level of response was observed in patients with disease duration of 3 years or less who were treated with combination therapy. The responses of the early RA group were consistent with those of the overall population.
Editorial Comment: These results are nearly identical to the one year results already published for the TEMPO group as a whole, although the radiographic results are not shown in this table. Most of the clinical trials with TNF antagonists have utilized a definition of "early" RA of less than 3 years duration. In contrast, the studies that have suggested that a delay in treatment may have worse outcomes utilized a more stringent definition of < 6 months duration. Whether there is a true "window of opportunity" in very early RA in which TNF antagonists are most effective remains to be studied. | |||||||||||||||||||||||||||||||||||||
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Objective: LTB4 is a chemoattractant for neutrophils. High concentrations of LTB4 have been found in synovial fluid and sera of patients with active RA. LTB4 receptor antagonists have been shown to reduce the severity of collagen-induced arthritis in mice. BIIL 284 is a potent, long-acting, oral antagonist of LTB4 receptors (both BLT-1 and BLT-2). A phase II clinical trial of BIIL 284 was undertaken to evaluate the efficacy and safety of BIIL 284 as monotherapy for the treatment of patients with active RA. Methods: 342 patients were randomized to receive either 5 mg (n = 80), 25 mg (n = 83), or 75 mg (n = 87) of BIIL 284 or placebo (n = 92). Concurrent DMARDs were not permitted, but stable doses of NSAIDS and low-dose corticosteroids were allowed. The duration of the study was 3 months. The primary endpoint was the percentage of patients with an ACR20 response. Results: Although at 3 months a higher percentage of ACR 20 responders was observed in the groups treated with 25 mg (28.9%) and 75 mg (28.7%) of BIIL 284 compared to placebo (18.5%), these differences were not statistically significant. Analysis of the individual components of the ACR 20 did not show any significant differences among the treatment groups. All trial treatments were safe and well tolerated. Conclusion: Treatment of patients with active RA with a potent long-acting LTB4 receptor antagonist produced only modest and statistically insignificant improvements in disease activity. The results of this trial suggest that LTB4 is not a major contributor to the inflammatory process in RA and is not a promising target for therapeutic intervention. Editorial Comment: This is the first study ever (to this reveiwer's knowledge) of a strategy to inhibit neutrophil activation for the treatment of RA. It has been estimated that as many as a million neutrophils ingress and egress an inflamed rheumatoid knee in a 24 hour period. The contribution of neutrophils to the inflammatory processes in RA remains unclear. Because neutrophils are chemoattracted to the synovial cavity (not the synovial tissue itself) where they directly contact the entire hyaline cartilage, it is conceivable that they play a major role in the degradation of cartilage. An inhibitor of neutrophil chemotaxis and/or activation might therefore be efficacious in RA. LTB4 is both a chemoattractant for, and activator of, PMNs and therefore an inhibitor of LTB4 might have efficacy in RA. The compound studied, BIIL 284, is a receptor antagonist of LTB4. This would be expected to suppress activation of PMNs. The absence of an effect of this drug in RA does not rule a role for PMNs in the pathogenesis of RA, however, since ingress of neutrophils may not be impeded. [It would have been interesting to measure synovial neutrophil counts in BIIL 284 vs placebo treated patients.] Furthermore, other stimuli of neutrophils such as C5a and interleukin-8 are also present in synovial fluid and would not be inhibited by an LTB4 receptor antagonist. | |||||||||||||||||||||||||||||||||||||
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Objective: The ligand for RANK (receptor activator of NF kappa B) plays a critical role in maturation and activation of osteoclasts and consequent bone resorption. AMG 162 is a fully human monoclonal antibody directed against RANK ligand (RANKL). The objective of this randominzed, double-blind study was to evaluate the efficacy and safety of AMG 162 in slowing loss of bone density. Methods: Postmenopausal women with low BMD (lumbar spine BMD T-score -1.8 to -4.0) were randomized to one of 9 treatment groups: Groups 1-7 received SQ injections of AMG 162 (6, 14, or 30 mg every 3 months or 14, 60, 100, or 210 mg every 6 months); Group 8 received placebo injections; Group 9 received open-label, 70-mg oral alendronate once weekly. The primary outcome was change in BMD by dual energy x-ray absorptiometry. The secondary outcome was change in bone biomarkers (serum C-telopeptide [CTX] and urine N-telopeptide [NTX]/creatinine). Patients had to be off bisphosphonates for one year before entering the study. Results: 411 women were enrolled (40-53 per group). Baseline demographic features, and baseline bone biomarker levels, were well balanced between the groups. Baseline mean (SD) age was 63 (8) years and lumbar spine T-score -2.2 (0.8). At 12 months, BMDs for the lumbar spine were: placebo, -0.8; alendronate, +4.6; AMG 162, +3-5.5 (alendronate vs placebo, and AMG 162 vs placebo, p<0.05). Dose-dependent increases in BMD with AMG 162 were observed as early as 1 month after dosing. AMG 162 (q 6 month) caused a rapid (within 72 hours) and sustained decreased in serum CTX. Decreases in serum CTX in all AMG 162 groups were significantly greater than alendronate (p < 0.0001) through month 2, and in the 3 highest AMG 162 dose groups through month 4. The response in urine NTX/creatinine confirmed the serum CTX response. AMG 162 was well tolerated. Dyspepsia was the most common adverse event in all groups, and occurred in 4%, 5%, and 20% of subjects in the placebo, AMG 162, and alendronate groups, respectively. One (0.3%) subject (14 mg AMG 162) had a transient, asymptomatic decrease in albumin-adjusted serum calcium below 8 mg/dL (7.8 mg/dL at 2 months). No other clinically meaningful laboratory changes occurred. Non-neutralizing anti-AMG 162 antibodies were detected at month 1 for 2 subjects, but did not persist. Conclusion: AMG 162 administered once every 6 months was well tolerated and caused a rapid, dose-dependent, decrease in bone turnover markers and a corresponding increase in BMD. Editorial Comment: This is an exciting study because it provides proof of concept for the importance of the RANKL molecule in bone resorption. However, these findings need to be corroborated with a decrease in fracture risk over the longer term. | |||||||||||||||||||||||||||||||||||||
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Purpose: A prior Phase II study of abatacept (CTLA4Ig) in RA patients who had disease activity despite methotrexate (MTX) showed moderate efficacy (NEJM 2003;349:1907). The current multicenter study was undertaken in a considerably larger group of patients to further test the efficacy and safety of abatacept in the same type of RA patients. Methods: RA patients with disease activity despite MTX treatment were randomized to abatacept 10 mg/kg versus placebo for one year, while continuing MTX. Treatment was administered on days 1, 15 and 29 and every 28 days thereafter. Co-primary endpoints were ACR20 response at 6 months and Genant-modified Sharp (radiological) score at 1 year. Results: 433 and 219 patients were randomized to abatacept and placebo, respectively. 88.9% and 74.0% of the abatacept and placebo groups, respectively, completed one year of the study. Baseline characteristics of the two groups were similar with average disease duration of ~8.6 years. ACR responses are shown below (p <0.001 for all comparisons of abatacept vs placebo):
At one year, 42.5% vs 9.9% of patients had low disease activity (DAS < 3.2) and 1.9% had DAS < 2.6 (DAS remission). Radiographic progression was significantly lower in the abatacept group compared to placebo for both erosions (p=0.029), joint space narrowing (p=0.009) and total score (p=0.012). Serious infections occurred in 3.9% of abatacept, and 2.3% for placebo, treated patients. Conclusion: Abatacept was efficacious and safe for the treatment of RA in patients with inadequate responses to MTX. Editorial Comment: Abatacept inhibits one of the co-stimulatory pathways of T cells. This study with abatacept builds on prior clinical trials with the drug in extending the (blinded) treatment time to 12 months, and in the addition of a radiological outcome. The ACR responses at 6 months are very comparable to the prior smaller Phase II study, even including the high placebo rate. However, it is interesting that ACR 50 and 70 responses continue to rise at 12 months and achieve levels that are very comparable to those of the TNF inhibitors. The radiological data confirm that abatacept is disease modifying. Unfortunately, a radiological scoring system was selected that is different from all of the TNF inhibitor studies; thus, a comparison of efficacy with these agents is difficult. Nonetheless, the data confirm that abatacept is an efficacious drug with a good safety profile at one year in RA patients receiving MTX. Abatacept provides a very promising alternative to TNF inhibitors in patients who have failed MTX. If and when abatacept is approved by the FDA, it will be interesting to see what the risk of infection is in the RA population in the community setting. | |||||||||||||||||||||||||||||||||||||
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Late Breaking Abstract #16: The ATTAIN Trial Abatacept (CTLA4Ig) Trial in the Treatment of Anti-TNF INadequate (RA) Responders Purpose: Prior studies with abatacept (CTLA4Ig) have demonstrated efficacy in patients with inadequate responses to methotrexate (MTX). This study was undertaken to evaluate the efficacy and safety of abatacept in patients with inadequate responses to TNF inhibitors. Methods: RA patients with an inadequate response to 3 months or more of treatment with a TNF inhibitor(s) were randomized to abatacept 10 mg/kg or placebo for six months. The TNF inhibitor had to have been discontinued (or washed out) prior to enrollment in the study. Patients were allowed to remain on one background DMARD. Study medication was administered on days 1, 15 and 29 and every 28 days thereafter. The primary endpoint was ACR20 response at 6 months. Results: 391 patients were enrolled. Baseline characteristics were similar between treatment groups. Mean disease duration was ~12 years, mean CRP 4.3; mean DAS28 6.9; mean swollen joint count 22. ACR responses at 6 months are shown below (p<0.005 or less for all comparisons):
DAS28 < 2.6 (DAS remission) was achieved in 10.0 vs 0.8% of abatacept and placebo patients, respectively (p<0.002). The incidence of serious infections was similar (2.3% for each group). Conclusion: Abatacept was efficacious and safe in RA patients who have had an inadequate response to a TNF inhibitor(s). Editorial Comment: These are remarkable responses in a patient population that is extremely recalcitrant to treatment. Abatacept (CTLA4Ig) is an inhibitor of one of the co-stimulatory pathways of T cell activation. It works, therefore, by a pathway that is totally different from the TNF inhibitors. These data are very exciting and offer promise to patients who have failed what is currently our best standard-of-care treatment (MTX + TNF inhibitor). | |||||||||||||||||||||||||||||||||||||
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ACR Special Abstract Vioxx Cardiovascular Safety Data from the APPROVe Study | |||||||||||||||||||||||||||||||||||||
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