Denver Arthritis Clinic

ABSTRACTThis study examines adult patients with severe, life-threatening anorexia nervosa who were admitted to an inpatient, medical stabilization unit between October 1, 2008 and December 31, 2014. Specifically, the study compares anorexia nervosa, binge purge subtype (AN-BP) and anorexia nervosa, restricting subtype (AN-R) on admission measures, hospital course, and outcomes. Of the 232 patients, 46% (N = 108) had AN-BP. Patients with AN-R manifested a higher frequency of underweight-mediated medical complications, including bone marrow dysfunction, hepatic dysfunction, and hypoglycemia. Understanding the pathophysiologic differences between severe AN-R and AN-BP is essential to understanding the abnormalities seen on clinical presentation, guiding appropriate clinical treatment, and predicting medical complications during refeeding.

Background Objectives To evaluate the effect of PEG sTNF-RI on the health related quality of life (HRQOL) of subjects with rheumatoid arthritis. Methods In a 12-week, multicenter, randomised, double-blind clinical trial, 194 subjects received either 400- or 800-mcg/kg of PEG sTNF-RI or placebo SC weekly (1:1:1). The study population included subjects with or without background DMARDs (combination therapy involving methotrexate with sulfasalazine or hydroxychloroquine, or sulfasalazine plus hydroxychloroquine). To measure HRQOL, the SF-36 was administered at baseline and at weeks 4 and 12. The SF-36 consists of 36 items designed to assess physical function (PF), role limitations due to physical problems (RP), body pain (BP), general health (GH), vitality/energy (VT), social function (SF), role limitations due to emotional problems (RE), and mental health (MH). The SF-36 is scored from 0 to 100, with higher scores indicating better HRQOL. Differences of 3 to 5 points are considered clinically and socially relevant. The mean change in each SF-36 scale score was compared between subjects receiving PEG sTNF-RI and those on placebo using a repeated measure mixed effect model analysis. The analysis set was a modified intent-to-treat sample, i.e. all patients who received at least one dose were included (n = 193). Results Subjects using either dose of PEG sTNF-RI experienced statistically significant, and clinically and socially relevant improvements in each SF-36 scale (see Table 1). These improvements exceeded those for subjects on placebo in every scale and were statistically significantly improved over placebo for 7 of 8 scales for the 800-mcg/kg dose, and 6 of 8 scales for the 400-mcg/kg dose. Conclusion Subjects receiving PEG sTNF-RI experienced statistically significant, clinically and socially relevant improvements in their SF-36 scores. These improvements occurred across a full range of health-related quality of life scales, from the physical to the psychosocial, and exceeded those for subjects on placebo. In this population of patients with rheumatoid arthritis, some of whom received DMARD or combination DMARD therapy, PEG sTNF-RI leads to significant and meaningful improvements in health-related quality of life.

Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown. We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months. Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale. On this scale, an increase of 1 point represents one new erosion or minimal narrowing. As compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, 50 percent, and 70 percent improvement in disease activity during the first six months (P<0.05). The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group (P= 0.001), and the respective increases during the first 12 months were 0.47 and 1.03 (P=0.002). Among patients who received the 25-mg dose of etanercept, 72 percent had no increase in the erosion score, as compared with 60 percent of patients in the methotrexate group (P=0.007). This group of patients also had fewer adverse events (P=0.02) and fewer infections (P= 0.006) than the group that was treated with methotrexate. As compared with oral methotrexate, subcutaneous [corrected] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis.

Mutations in one of the two genes encoding type I procollagen (COL1A1 and COL1A2) are frequently the cause of osteogenesis imperfecta (OI), a disorder characterized by brittle bones. Here we tested whether patients with low bone density also have mutations in these genes. The 26 patients studied had no apparent metabolic bone disease, but most had a positive family history of osteopenia or osteoporosis. Although a diagnosis of OI was considered by the clinician in some cases, the clinical criteria for OI were not satisfied. Our strategy for mutation analysis consisted of PCR amplification of cDNA made to fibroblast mRNA using primers specific for the coding regions of COL1A1 and COL1A2. The PCR products were then sequenced directly with primers located within each PCR product. We found that 3 of 26 patients had mutations that altered the encoded amino acid. One mutation, at position alpha 2(I)-661 has been reported (Spotila et al. 1991 Proc Natl Acad Sci USA PNAS 88:5423). The other 2 patients, who were not related to each other, had a mutation that altered the proline codon at alpha 1(I)-27 to alanine. This mutation was not found in 81 normal individuals or in 37 additional osteopenic individuals. However, its effect on the biologic function of type I collagen, as well as its role in osteopenia, is uncertain. In addition to the two mutations, we found a polymorphism in codon alpha 2(I)-459. Although this polymorphism involved an amino acid substitution, it was present with equal frequency in the patient and the normal population. By analyzing this and previously reported neutral sequence variants in the COL1A2 gene, we determined that all patients expressed both alleles of the COL1A2 gene. The 12 patients who were heterozygous for a COL1A1 neutral sequence variant also expressed both alleles. Here we present all PCR primer and sequencing primer information. The results suggest that surveying a larger group of similarly selected individuals may reveal additional mutations in the COL1A1 or COL1A2 genes.

Weekly treatment with low-dose oral methotrexate (MTX) was compared with daily auranofin (AUR) treatment in a 36-week double-blind, randomized, multicenter study of 281 patients with active, adult-onset rheumatoid arthritis. Both treatment groups showed significant improvement by the usual measures of clinical efficacy. The response with MTX occurred earlier and was consistently greater than that with AUR. An intent-to-treat analysis showed significantly greater improvement (P less than 0.01) with MTX for painful and swollen joint counts and physician and patient global assessments of disease activity. Adverse reactions were reported more frequently in the AUR group, and more AUR-treated patients were withdrawn from the study because of toxicity. MTX was thus more effective and better tolerated than AUR in this study.