American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) 2010 Annual Scientific Meeting

American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) 2010 Annual Scientific Meeting
November 6-11, 2010 Atlanta, GA

Posters

Febuxostat Versus Allopurinol for Gout: A Subgroup Analysis of the CONFIRMS Trial
Atlanta, GA—In a subset analysis of 374 elderly subjects (≥65 years) with gout and serum urate levels ≥8.0 mg/dL from the CONFIRMS trial (https://bit.ly/CONFIRMS), researchers concluded that treatment with febuxostat (FEB; a nonpurine xanthine oxidase inhibitor for the treatment of hyperuricemia in persons with chronic gout) was well tolerated and reduced serum urate levels to <6.0 mg/dL in a higher proportion of participants than did allopurinol (ALLO). The CONFIRMS trial randomized a total of 2269 subjects with gout and serum urate levels ≥8.0 mg/dL to FEB 40 mg or 80 mg or to ALLO 200mg or 300 mg (the 200 mg dose was used in those with moderate renal impairment) once daily for 6 months. Results of this subgroup analysis were presented in a poster session at the ACR/ARHP annual meeting. Eswar Krishnan, MD, Stanford University, Stanford, CA, and colleagues also found that the response in subjects with moderate renal impairment was statistically significantly better with either dose of FEB as compared with ALLO.

The three treatment groups were similar in age, gender, race, duration of gout, and baseline characteristics and comorbidities. Subjects (mean age, 71 years) were predominantly male (86%), white (85%), and obese (51% with body mass index ≥30 kg/m2). The mean baseline serum urate level was 9.4 mg/dL and the mean duration of gout was 15 years. At baseline, 82% of subjects had hypertension, 25% had diabetes, 24% had coronary artery disease, 21% had cardiac arrhythmias, and 11% had previous myocardial infarction. A history of kidney stones was present in 20% of subjects, and a history of tophi was present in 19%. In addition, some degree of renal impairment was present in 98% of subjects.

FEB 40 mg was given to 115 persons, FEB 80 mg was given to 128 persons, and ALLO was given to 131 persons. In addition to FEB or ALLO, gout flare prophylaxis with colchicine or naproxen was also provided for the entire study duration. The primary efficacy end point was percentage of participants achieving serum urate levels <6.0 mg/dL at the final study visit. A secondary efficacy end point was the proportion of participants with mild or moderate renal impairment with a final serum urate level <6.0 mg/dL. Safety was also assessed in this high-risk population.

The study results are as follows: the proportions of participants with final serum urate levels <6.0 mg/dL were 62% (71/115) in the FEB 40-mg group, 82% (105/128) in the FEB 80-mg group, and 47% (62/131) in the ALLO group, respectively. Researchers found that FEB 80 mg was significantly more efficacious than ALLO in participants with mild renal impairment (P = .004), and was superior to both FEB 40 mg and ALLO in subjects with moderate renal impairment (P ≤ .001). The percentage of participants receiving FEB 40 mg who achieved a final serum urate <6.0 mg/dL with either mild or moderate renal impairment, although not statistically significant, was numerically greater than that of the ALLO group. It was reported that the majority of adverse events were transient and resolved while the subjects were receiving treatment. Diarrhea (10%) and upper respiratory infection (8%) were the most frequently reported adverse events, irrespective of treatment. In addition, 8% of subjects in the FEB 40-mg group, 6% in the FEB 80-mg group, and 11% in the ALLO group reported serious adverse events; the most common serious adverse events were cardiac disorders (1%, 2%, and 3% in the FEB 40-mg, FEB 80-mg, and ALLO groups, respectively) and lower respiratory tract infections (1%, 0%, and 2% in the FEB 40-mg, FEB 80-mg, and ALLO groups, respectively). It was noted that no hypersensitivity reactions were reported by any participants. Researchers confirmed that overall response rates reported in this subgroup were similar to those reported in the total CONFIRMS trial population.

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Prescribing for Rheumatoid Arthritis Leaves Much to Be Desired
Atlanta, GA—Many patients with rheumatoid arthritis (RA) are not being treated appropriately, according to two studies presented at the ACR/ARHP annual meeting. The first study showed that only about half of all RA patients with high disease activity or moderate disease activity with a poor prognosis are being treated according to the 2008 ACR guidelines. The second study found that one-third of Medicare patients with RA were not receiving any disease-modifying antirheumatic drugs (DMARDs).

The first study was based on the CORRONA (Consortium of Rheumatology Researchers of North America) registry of approximately 23,000 patients treated by rheumatologists. Most patients with low disease activity were receiving therapy consistent with ACR guidelines; however, only 42% of those with moderate disease activity and 50% of those with high disease activity were receiving treatment commensurate with ACR-recommended treatment, said lead author Leslie R. Harrold, MD, University of Massachusetts Medical School, Worcester. “The study suggests that publication of the guidelines did not change rheumatologists’ prescribing patterns,” Dr. Harrold indicated.

The study included biologic-naïve RA patients cared for by U.S. rheumatologists participating in the CORRONA registry between 6 and 18 months after the guidelines were published. Among methotrexateonly users, 91% to 95% of those with low disease activity scores and 79% to 89% of those with moderate disease activity scores and good prognosis were receiving nonbiologic DMARDs. Among those with moderate disease activity and poor prognosis, 34% to 38% were receiving care consistent with the guidelines. Among those with high disease activity, approximately 44% were receiving care consistent with the guidelines. In multiple nonbiologic DMARD users, 44% to 53% of those with moderate disease activity had guideline-consistent care, and 50% to 53% of those with high disease activity received guideline-consistent care.

The second study was based on records for approximately 93,000 Medicare beneficiaries with RA included in the Healthcare Effectiveness Data and Information Set (HEDIS). Gabriela Schmajuk, MD, Stanford University, Palo Alto, CA, reported that approximately 35,000 patients (38%) were not receiving conventional or biologic DMARDs in 2008.

The study found a wide variation in DMARD use among 245 health plans providing HEDIS data, ranging from 13% to 91%. Health maintenance organization plans instituted after 1999 were more likely to be low-performing plans with low use of DMARDs, Dr. Schmajuk continued, even after adjusting for other characteristics. Factors strongly associated with low DMARD use included age ≥85 years (41.5% used DMARDs), male gender (60.9% used DMARDs), nonwhite race (black persons, 56.6%; other nonwhite persons, 58.2%), low income (55%), geographic region (Mid-Atlantic or South Atlantic, >50%), and health professional shortage area (62%).

The percentage of those receiving guideline-recommended drugs did increase overtime, she commented. In 2005, 41% of Medicare recipients with RA in the HEDIS database were not receiving biologic or nonbiologic DMARD therapy, and in 2008, about 20% of patients with RA failed to have DMARD treatment.

The authors emphasized that quality improvement initiatives are needed so that older patients with RA in low-performing plans and areas of the country receive recommended treatment.

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Ibuprofen/Famotidine Versus Ibuprofen Alone in Chronic NSAID Users
Atlanta, GA—A combination tablet of ibuprofen plus high-dose famotidine (a gastroprotectant) dubbed HZT-501 reduces gastrointestinal (GI) ulcers overall in chronic nonsteroidal anti-inflammatory drug (NSAID) users as well as in a subset of NSAID users also taking low-dose aspirin, as compared with ibuprofen alone, according to pooled results of two, 24-week, double-blind, controlled trials reported in a poster at the ACR/ARHP meeting. The combination of prescription-strength ibuprofen and high-dose famotidine (unavailable in a single pill) in one tablet reduced ulcers by 50%, said the authors.

Gastroprotection is important in chronic NSAID users, especially in those who also take low-dose aspirin. Famotidine 40 mg/day has been shown to provide gastroprotection in low-dose aspirin users similar to that provided by double doses of H₂ receptor antagonists (https://bit.ly/FAMOUSTrial).

REDUCE-1 and REDUCE-2 (Registration Endoscopic Study to Determine Ulcer Formation of HZT- 501 Compared to Ibuprofen: Efficacy and Safety Study) randomized 1533 patients taking NSAIDs for pain due to osteoarthritis, rheumatoid arthritis, chronic low back pain, chronic regional pain syndrome, and/or chronic soft tissue pain to receive either HZT-501 (n = 1022) or ibuprofen (n = 511) for 24 weeks. Low-dose aspirin users numbered 121 in the HZT-501 group and 79 in the ibuprofen group. To be included in the study, participants were required to take daily NSAIDs for >6 months and to have no history of ulcer complications, to be Helicobacter pylori–negative, and to be endoscopy-negative for ulcers at baseline, but they could have less than five erosions in the GI tract. The populations of both REDUCE-1 and REDUCE-2 were well balanced for demographic characteristics. Mean age was 55 years, approximately 18% were ≥65 years of age, approximately 66% were women, and approximately 6% had a prior ulcer. REDUCE-1 had a slightly higher percentage of low-dose aspirin and antithrombotic/anticoagulant users, as well as GI erosions.

Patients were evaluated at weeks 8, 16, and 24 with repeat endoscopy, physical examination, assessment for adverse events, and concomitant medications. Laboratory tests and tablet counts were also evaluated at these time points.

In a pooled analysis of results, HZT-501 was significantly superior to ibuprofen: the percentage of patients with upper GI ulcers according to cumulative crude proportion at week 24 overall was 11% for HZT-501 versus 21.9% for ibuprofen alone (P < .0001). Similar gastroprotection according to cumulative crude proportion at week 24 was observed in the subset of low-dose aspirin users: upper GI ulcers were reported in 12.8% versus 32.8%, respectively (P = .002). A forest plot for the relative risks of upper GI ulcers in the two treatment groups favored the combination tablet over ibuprofen for all subgroups, including age <65 or ≥65 years, prior ulcer or no prior ulcer, low-dose aspirin or no low-dose aspirin, and sex. The percentage of patients with treatment- emergent adverse events significantly favored the combination tablet: 31% versus 42.9%, respectively (P < .0001). Lower incidence of discontinuations and dyspepsia was observed with HZT-501 versus ibuprofen: dyspepsia was reported in 4.7% of the HZT-501 group versus 8% of the ibuprofen group (P = .009).