Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

Background and objectives

Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission.

Design, setting, participants, & measurements

A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined.

Results

In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population.

Conclusion

This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted.     

Management of hypertension in women

A gender-specific approach to cardiovascular (CV) diseases has been practiced for decades, although not always to the advantage of women. Based on population data showing that women are at lower risk for CV events than men female gender has generally been regarded as a protective factor for CV disease. Unfortunately, CV risk assessment has therefore received less attention in women. Despite the lower absolute risk of CV events in women compared with age-matched men, the majority of women die from CV diseases. In absolute numbers, since 1984, more women than men died of CV disease each year. Most CV events occur in women with known traditional CV risk factors. Improving risk factor management in women of all ages therefore yields an enormous potential to reduce CV morbidity and mortality in the population. Aside from smoking cessation, hypertension (HTN) control is the single most important intervention to reduce the risk of future CV events in women. This review highlights peculiarities of HTN as they pertain to women, and points out where diagnosis and management of HTN may require a gender-specific focus.     

Peri-operative second molar tube failure during orthognathic surgery: two case reports

With improvements in bonding techniques, bracket base design and bond strengths, molar tubes are becoming more popular in orthodontics. Molar tubes make an attractive alternative to conventional banding due to a reduction in clinical bonding time and ease of placement on partially erupted teeth. The use of molar tubes negates the need for orthodontic separation and subsequent cementation of bands, and offers improved periodontal health. Their use on terminal molars, however, should be limited to non-orthognathic cases. This paper presents two cases of peri-operative second molar tube failure during orthognathic surgery. They are presented in the hope that it will highlight the importance of banding the distal terminal molar in orthognathic cases to prevent loss of molar tubes and peri-operative contamination of the surgical wound site.     

Epidemiology of human T cell leukemia virus type I infection in East Sepik Province, Papua New Guinea

A serological survey of 317 healthy residents of rural Papua New Guinea (PNG) showed a 26% prevalence of antibodies to human T cell leukemia virus type I (HTLV-I). Antibody to HTLV-I was detected in 16% of children less than or equal to 10 years old (including an 18-month-old child) and increased to greater than or equal to 24% in subjects greater than 20 years old. Prospective examination for antibody in 104 residents of one village revealed a seroconversion rate of 13% over a one-year period. The mean titer of antibody in these subjects (1:183) was lower (P less than .0005) than that in persons who were persistently seropositive (1:718). Analysis for clustering of infected subjects suggested that personal contact within the home played a role in the horizontal spread of HTLV-I. These data indicate that HTLV-I infection has a higher prevalence in PNG than in other endemic parts of the world, exposure occurs at an early age, and infection and/or seroconversion is common in adults as well as in children.     

Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals

The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV- I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported.