December 2008 • www.rheumatologynews.com Arthritis 11 Allopurinol Failures Respond Well to Pegloticase

BY SHERRY BOSCHERT study achieved this goal in the intent-to-treat analysis, ac- A physician in the audience challenged this assumption, San Francisco Bureau cording to Dr. Sundy. saying the events should occur in the placebo group, too, However, on a regimen of pegloticase every 2 weeks, if that were the case. S AN F RANCISCO — The investigational drug pe- 47% of the patients in GOUT1 and 38% of patients in A current, ongoing 12-month open-label extension of gloticase significantly reduced serum urate levels com- GOUT2 were treated successfully. the study might soon shed some light on this, Dr. Sundy pared with placebo in two randomized, double-blind On a treatment regimen of pegloticase every 4 weeks, said. studies of 212 patients with gout who had previously 20% of GOUT1 patients and 48% of GOUT2 patients Secondary measures of efficacy in the double-blinded failed treatment with allopurinol. achieved successful improvements, reported Dr. Sundy, studies found clinically and statistically significant im- Patients received intravenous infusions of placebo or who is a rheumatologist at Duke University, Durham, provements in the pegloticase groups compared with 8 mg pegloticase (Puricase) every 2 N.C., and his associates. placebo. or 4 weeks in the 24-week Gout Regimens of pegloticase The serum urate improvements Among patients with at least one tophus who were Outcome and Urate Therapy stud- that were seen with both of the pe- evaluated by computer-assisted photographic analysis, a ies (GOUT1 and GOUT2), the re- every 2 weeks and gloticase regimens were significant tophus resolved completely in 21 (40%) of 52 patients get- sults of which were presented by pegloticase every 4 weeks compared with placebo, he com- ting pegloticase every 2 weeks and 11 (21%) of 52 patients Dr. John S. Sundy at the annual mented. getting pegloticase every 4 weeks, compared with 1 (4%) meeting of the American College of rendered significant Dr. Sundy disclosed that the com- of 27 patients on placebo. Rheumatology. improvements in patients’ pany that makes pegloticase, Savient The number of tender joints decreased by seven in the At baseline, all patients had a Pharmaceuticals, both funded the 2-week pegloticase group and by six in the 4-week group serum urate level that was higher serum urate levels. study and has given research funds compared with an average decrease of one tender joint than 8 mg/dL (an average of 10 or other payments to Dr. Sundy and on placebo. The number of swollen joints did not differ mg/dL) and severe, symptomatic gout, with three or many of the other investigators on this study, some of significantly between groups. more gout flares in the previous 18 months (an average whom are Savient employees. Both pegloticase groups, but not the placebo group, of 10 flares), one or more tophi (present in 73% of pa- Additionally, Duke University and one of its employ- showed significant improvements in the Short Form–36 tients), or chronic gouty arthropathy (present in 58% of ees who was not involved in the study hold patents on Health Survey physical component summary score and patients in the studies). pegloticase. the physical functioning subscale of the Health Assess- The patient cohort had had gout for a mean of 15 years. A total of eight serious cardiovascular events occurred ment Questionnaire–Disability Index. Allopurinol treatment was contraindicated or had in patients getting pegloticase: two cardiac arrests, two The study cohort was 82% male, with a mean age of failed to reduce serum urate to below 6 mg/dL in these exacerbations of heart failure leading to death in one pa- 55 years and a high degree of comorbidity. patients. tient, two dysrhythmias, one myocardial infection, and Hypertension was present in 72% of patients, chronic Treatment in the study was considered successful if a one case of angina. kidney disease in 30%, diabetes in 22%, hypercholes- patient’s uric acid readings were within the normal range Among other side effects, infusion reactions led to dis- terolemia in 21%, and coronary artery disease in 11% of (less than 6 mg/dL) at least 80% of the time in months continuation of treatment in 11%-13% of patients on pe- the patients. 3 and 6 of the studies. gloticase and none on placebo. Pegloticase is a recombinant mammalian urate oxidase None of the patients in the placebo groups of either Dr. Sundy said the cardiovascular events “may reflect modified with polyethylene glycol that converts urate to the 104-patient GOUT1 study or the 108-patient GOUT2 underlying comorbidity.” allantoin. ■ Profoundly Lower Left Ventricular Mass Seen in RA Patients

BY BETSY BATES participants in the Multi-Ethnic Study of “In fact, the mean left ventricular mass No characteristics were associated with Los Angeles Bureau Atherosclerosis who did not have RA. was lower in 45-year-old RA patients than ejection fraction. None of the members of either group mean left ventricular mass in 80-year-old The study findings raise intriguing ques- S AN F RANCISCO — Patients with had a history of cardiovascular events or control patients, regardless of gender,” tions about whether rheumatoid arthritis rheumatoid arthritis have a “markedly” procedures. Dr. Giles commented during his podium and its treatment heighten patients’ car- lower mean left ventricular mass than do The rheumatoid arthritis cohort was presentation. diovascular risk through different mecha- age-matched controls, a finding that pro- younger than was the control group Left ventricular stroke volume was nisms than in the general, non-RA popu- vides what may be a significant clue to el- (mean age 59, compared with 63), and was marginally lower in RA patients than in lation, said Dr. Giles. evated cardiovascular mortality in this also less likely to have a diagnosis of dia- controls, significantly so in men. For example, markedly lower left ven- population, according to a group of Mary- betes (4% versus 14%) or hypertension “Small but significant” reductions in ad- tricular mass may reflect the “afteref- land researchers. (32% versus 49%). justed mean ejection fraction were seen as fects” of subclinical myocarditis. The specific mechanisms underlying However, the patients’ mean unadjust- well, Dr. Giles said. On the other hand, lower left ventric- cardiovascular risk are only now being ed left ventricular mass was 18% lower No differences were seen in RA patients ular mass measurements “may support fully explored in this population, in part (120 g/m2 compared with 147 g/m2), a and controls with regard to adjusted mean the concept that RA is a disorder of ac- because RA patients often fail to present difference that remained significant (at end diastolic volume. celerated aging,” he said. with the classic early signs and symptoms 14%) after subsequent adjustment for The Johns Hopkins team also explored Dr. Giles and his associates reported of cardiac disease, commented Dr. Jon body surface area, age, gender, race, potentially significant associations be- having no financial conflicts of interest Giles, who is a rheumatologist at the blood pressure, antihypertensive use, cho- tween cardiovascular risk markers and RA with regard to this study. ■ Johns Hopkins Division of Rheumatol- lesterol and triglyceride levels, diabetes, disease characteristics such ogy in Baltimore, in a presentation given and exercise. as disease severity, activity, at the recent annual meeting of the The difference was particularly pro- treatment, and systemic in- Mean Adjusted Left Ventricular Mass American College of Rheumatology. nounced for male patients with RA, whose flammation. RA patients (n = 75) For example, Dr. Giles cited heart fail- mean adjusted left ventricular mass was They found only two 172 g/m2 ure rates that are “nearly doubled” in RA found to be fully 19% lower than that of factors that were indepen- Controls (n = 775) patients. men who did not have a rheumatoid dently associated with left 139 g/m2 Yet, “little is known about the myocar- arthritis diagnosis. ventricular mass, stroke 125 g/m2 dial changes that precede clinical heart fail- Female rheumatoid arthritis patients volume, and end diastolic 114 g/m2 ure in these patients,” he said. had a 9% lower left ventricular mass than volume in rheumatoid Dr. Giles and his associates turned to did women without the inflammatory arthritis patients. EWS cardiac MRI, a highly sensitive tool for as- disease. One factor was in- N sessing left ventricular structure and func- In both the RA and control groups, creased anti–cyclic citrulli- tion, to hunt for preclinical risk factors for mean left ventricular mass decreased with nated peptide antibodies. EDICAL heart failure. age. The other was the use M

Rheumatoid arthritis patients with However, it was lower in rheumatoid of biological disease-mod- Men Women LOBAL moderate disease (average 7 years’ dura- arthritis patients than in controls in every ifying drugs (predomi- G tion) who enrolled in the ESCAPE RA age group, including the youngest patients nantly tumor necrosis fac- Source: Dr. Giles LSEVIER trial (n = 75) were compared with 775 in the study. tor–D inhibitors). E