This study was designed to assess the efficacy and safety of pregabalin-a novel alpha(2)-delta ligand with analgesic, anxiolytic, and anticonvulsant activity-for treating neuropathic pain in patients with post-herpetic neuralgia (PHN). Two hundred and thirty-eight patients were randomised into this multicentre, doubleblind, placebo-controlled trial to receive 150 (n=81), 300 mg/day (n=76) pregabalin, or placebo (n=81) for 8 weeks. Among the exclusion criteria was failure to respond to previous treatment for PHN with gabapentin at doses > or =1200 mg/day. Endpoint mean pain scores were significantly reduced in patients receiving 150 or 300 mg/day pregabalin compared with placebo. Efficacy was observed as early as week 1 and was maintained throughout the study. Significantly more patients in both pregabalin groups (150 mg, 26%; 300 mg, 28%) were responders (> or =50% decrease in mean pain score from baseline to endpoint) than in the placebo group (10%). Additionally, by week 1 and for the study's duration, 150 and 300 mg/day pregabalin significantly reduced weekly mean sleep interference scores. More pregabalin-treated patients than placebo-treated patients reported that they were 'much improved' or 'very much improved'. Health-related quality-of-life (HRQoL) measurements using the SF-36 Health Survey demonstrated improvement in the mental health domain for both pregabalin dosages, and bodily pain and vitality domains were improved in the 300 mg/day group. The most frequent adverse events were dizziness, somnolence, peripheral oedema, headache, and dry mouth. Pregabalin efficaciously treated the neuropathic pain of PHN. Additionally, pregabalin was associated with decreased sleep interference and significant improvements in HRQoL measures.

Objective. To assess the safety and tolerability of atacicept in patients with systemic lupus erythematosus (SLE) and the biologic effect of atacicept on B lymphocyte and immunoglobulin levels. Atacicept is a TACI-Ig fusion protein that inhibits B cell stimulation by binding to B lymphocyte stimulator and a proliferationinducing ligand.Methods. This phase Ib, double-blind, placebocontrolled, dose-escalating trial comprised 6 cohorts of patients treated with atacicept or placebo in a 3:1 ratio of active drug to placebo (n ‫؍‬ 8 per group; n ‫؍‬ 7 in cohort 5). Cohorts 1-4 received a single subcutaneous dose of placebo or either 0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 9 mg/kg of atacicept. Cohorts 5 and 6 received weekly doses of placebo or either 1 mg/kg or 3 mg/kg of atacicept for 4 weeks. Patients were followed up for 6 weeks (cohorts 1-4) or 9 weeks (cohorts 5 and 6). Patients with mild-to-moderate SLE were enrolled.Results. Biologic activity of atacicept was demonstrated by dose-dependent reductions in immunoglobulin levels and in mature and total B cell numbers. This effect was most pronounced in the repeated-dose cohorts and was sustained throughout the followup period. There were no changes in the numbers of T cells, natural killer cells, or monocytes. Mild injection-site reactions occurred more frequently among the atacicept group than the placebo group. There were no differences in the frequency or type of adverse events and no severe or serious adverse events in patients treated with atacicept.Conclusion. Atacicept administered subcutaneously was well tolerated and demonstrated biologic activity consistent with the proposed mechanism of action.Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by the pro-

Objective. To assess the efficacy, safety, and biologic activity of atacicept in tumor necrosis factor antagonist-naive patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate.Methods. In this phase II study, patients with active RA (n ‫؍‬ 311) were randomized 1:1:1:1 to receive placebo, atacicept 150 mg weekly with or without a 4-week loading period (twice-weekly dosing), or openlabel adalimumab 40 mg every other week, for 25 weeks. The primary end point was 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP), at week 26. Secondary end points included additional assessments of efficacy, biologic activity, and safety.Results. The proportion of patients meeting the primary end point (ACR20-CRP response) did not differ significantly in the atacicept groups and the placebo group (46% in the placebo group, 45% in the atacicept loading group, and 58% in the atacicept nonloading group). In contrast, an ACR20-CRP response was observed in 71% of patients in the adalimumab group (P < 0.001 versus placebo). ACR50-CRP response rates were significantly higher in all activetreatment groups compared with placebo, but ACR70-CRP response rates were superior only in the adalimumab group. Atacicept treatment reduced the levels of serum IgG, IgA, and IgM rheumatoid factor and the levels of circulating mature B cells and plasma cells. The effects of treatment were similar with and without loading. Immunoglobulin levels returned toward baseline values during the treatment-free followup period (week 38). The most frequent adverse events associated with atacicept represented common illnesses. No serious infections occurred among patients treated with atacicept.Conclusion. The primary end point (ACR20-CRP response) was not met despite significant biologic effects of atacicept that were consistent with its proposed mechanism of action. Modest effects of atacicept were seen for some secondary efficacy end points. Treatment with atacicept raised no new safety concerns.

No abstract

No abstract