Twice daily versus once nightly dosing of pregabalin for fibromyalgia: a double-blind randomized clinical trial of efficacy and safety.

OBJECTIVE: To compare the efficacy, discontinuation rates, and safety of once nightly versus twice daily dosing of pregabalin in a community-based trial. METHODS: This multicenter, double-blind, 8-week randomized clinical trial compared the effects of 300-mg daily doses of pregabalin given either twice daily or once nightly for the treatment of fibromyalgia in 177 patients. The primary outcome was the comparison of end point mean pain scores derived from a daily diary. RESULTS: Both twice daily (88 patients randomized) and once nightly (89 patients) pregabalin significantly reduced the average severity of pain experienced by patients (P < 0.001 for both). Treatment-emergent adverse events were reported by significantly more patients in the twice daily group than those in the once nightly group (P = 0.023). There were no significant differences between the groups for the frequencies of individual adverse events (P > 0.05 for all). There was no significant difference in adverse events or efficacy in patients taking both pregabalin and a selective serotonin and norepinephrine reuptake inhibitor or selective serotonin uptake inhibitor. CONCLUSION: While a nightly dosing schedule of pregabalin has been used by clinicians hoping to improve treatment, this study showed no significant difference (either beneficial or detrimental) between either treatment option. While there was a decrease in total patient-reported adverse events in the once nightly arm, the lack of specificity in relation to a particular adverse event suggested no real difference in adverse events.

Oral calcitonin.

Both injectable and nasal spray calcitonins have been utilized in the treatment of postmenopausal osteoporosis for over 25 years. More widespread use of calcitonin in the treatment of osteoporosis has been hampered in part due to poor patient acceptability and compliance and the inability of patients to take this medication as an oral pill. In recent years, an oral preparation of calcitonin has been developed that combines the active peptide hormone with a caprylic acid derivative to enhance bioavailability. Clinical trials with oral calcitonin in patients with osteoarthritis are currently being conducted. A recent phase 3 study failed to demonstrate significant vertebral fracture reduction, and as a result the clinical program for oral calcitonin in osteoporosis is under review for further consideration.

Safety, tolerability, and clinical outcomes after intraarticular injection of a recombinant adeno-associated vector containing a tumor necrosis factor antagonist gene: results of a phase 1/2 Study.

OBJECTIVE: To assess safety and clinical outcomes in patients with inflammatory arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant adeno-associated viral vector containing the human tumor necrosis factor (TNF) receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene. METHODS: In this phase 1/2 randomized study, adults with persistent moderate or severe inflammation in a target joint, being treated with or without systemic anti-TNF therapy, received a single IA injection of either rAAV2-TNFR:Fc (1 x 10(11), 1 x 10(12), or 1 x 10(13) DNase-resistant particles/ml joint volume) or placebo, followed by open-label rAAV2-TNFR:Fc 12-30 weeks later, depending on when the target joint met predetermined criteria for reinjection. RESULTS: 127 subjects received the first injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc. Administration site reactions, consisting of transient mild to moderate increases in tenderness and swelling of the injected joint, occurred after 23/191 (12%) rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events were not dose-dependent. Notable serious adverse events (SAE) included culture-negative septic arthritis in a subject receiving leflunomide and fatal disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in target joint global visual analog scale was observed in 21/50 (42%) rAAV2-TNFR:Fc subjects and 3/16 (19%) placebo subjects 12 weeks after first injection (p = 0.14). CONCLUSION: IA rAAV2-TNFR:Fc resulted in administration site reactions after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered not related to study agent. Patient-reported outcome measures of clinical response showed greater improvement in treated patients than placebo patients.

Osteoporosis in men.

Osteoporosis in men is now recognized as an increasingly important public health issue. About 30 percent of hip fractures occur in men, and one in eight men older than 50 years will have an osteoporotic fracture. Because of their greater peak bone mass, men usually present with hip, vertebral body, or distal wrist fractures 10 years later than women. Hip fractures in men, however, result in a 31 percent mortality rate at one year after fracture versus a rate of 17 percent in women. Major risk factors for osteoporosis in men are glucocorticoid use for longer than six months, osteopenia seen on plain radiographs, a history of nontraumatic fracture, hypogonadism, and advancing age. Bisphosphonates and teriparatide (recombinant parathyhroid hormone) have recently been approved for use in men and should be considered along with supplemental calcium and vitamin D. Increased awareness by physicians of risk factors for male osteoporosis--and early diagnosis and treatment--are needed to decrease the morbidity and mortality resulting from osteoporotic fractures.

Position statements of the International Society for Clinical Densitometry: methodology.

Given the need for authoritative positions in areas of controversy in the field of bone densitometry, the International Society for Clinical Densitometry (ISCD) convened a Position Development Conference in Denver, CO, USA, in July 2001. Four general areas were selected on the basis of clinical importance and likelihood of reaching agreement. These areas were discussed at length prior to the conference by the Scientific Advisory Committee of the ISCD and presented to a panel of experts at the conference. The four areas included discussions of (1). the regions of interest of central dual X-ray densitometry (DXA), (2). the criteria by which a densitometric diagnosis of osteoporosis can be made in men and non-Caucasian women, (3). the role of serial BMD measurements in patient management, and (4). the standards by which bone mass measurements at peripheral sites should be used in the diagnosis of osteoporosis. Details of the methodology used at the conference are discussed. The following papers explain the results of the discussions and describe the official ISCD positions.