B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use

The development of B cell-targeted biologics represents a major advance in the treatment of autoimmune rheumatic diseases. As with other immunosuppressive agents, risk of infection is a key clinical concern. This review summarises safety data from 15 years of experience of rituximab in autoimmune diseases with a particular focus on opportunistic infection and class-specific complications and infection risk. Rarely, cases of progressive multifocal leucoencephalopathy in rituximab-treated patients (5/100 000) have accumulated over time although no proven causal association has yet been shown. With repeat cycles of therapy, hypogammaglobulinaemia has been observed in a larger proportion of patients and is associated with increased risk of serious infections. The infection profile of the newer B cell-targeted agent, belimumab, in patients with active systemic lupus erythematosus is also discussed. Data from registries are needed to extend insights further and also to evaluate for any impact with the difference in mode of action of belimumab and infection risk in this population

Regional disparities in infant mortality in Canada: a reversal of egalitarian trends

<p>Abstract</p> <p>Background</p> <p>Although national health insurance plans and social programs introduced in the 1960s led to reductions in regional disparities in infant mortality in Canada, it is unclear if such patterns prevailed in the 1990s when the health care and related systems were under fiscal duress. This study examined regional patterns of change in infant mortality in Canada in recent decades.</p> <p>Methods</p> <p>We analysed regional changes in crude infant mortality rates and in infant mortality rates among live births with a birth weight ≥ 500 g and ≥ 1,000 g in Canada from 1945 to 2002. Associations between baseline infant mortality rates in the provinces and territories (e.g., in 1985–89) and the change observed in infant mortality rates over the subsequent period (e.g., between 1985–89 and 1995–99) were assessed using Spearman's rank correlation coefficient. Trends in regional disparities were also assessed by calculating period-specific rate ratios between provinces/territories with the highest versus the lowest infant mortality.</p> <p>Results</p> <p>Provincial/territorial infant mortality rates in 1945–49 were not correlated with changes in infant mortality over the next 10 years (rho = 0.01, P = 0.99). However, there was a strong negative correlation between infant mortality rates in 1965–69 and the subsequent decline in infant mortality (rho = - 0.85, P = 0.002). Provinces/territories with higher infant mortality rates in 1965–69 (Northwest Territories 64.7 vs British Columbia 20.7 per 1,000 live births) experienced relatively larger reductions in infant mortality between 1965–69 and 1975–79 (53.7% decline in the Northwest Territories vs a 36.6% decline in British Columbia). This pattern was reversed in the more recent decades. Provinces/territories with higher infant mortality rates ≥ 500 g in 1985–89 experience relatively smaller reductions in infant mortality between 1985–89 and 2000–02 (rho = 0.82, P = 0.004). The infant mortality ≥ 500 g rate ratio (contrasting the province/territory with the highest versus lowest infant mortality) was 3.2 in 1965–69, 2.4 in 1975–79, 2.2 in 1985–89, 3.1 in 1995–99 and 4.1 in 2000–02.</p> <p>Conclusion</p> <p>Fiscal constraints in the 1990s led to a reversal of provincial/territorial patterns of change in infant mortality in Canada and to an increase in regional health disparities.</p

Patients’ experiences of lupus related foot problems : a qualitative investigation

Background: Systemic lupus erythematosus (SLE) can present with a variety of symptoms. Previous research has shown there is a high prevalence of lower limb and foot problems in patients with SLE associated with the musculoskeletal, vascular and neurological changes. Furthermore, there is a high prevalence of infections affecting the feet and a range of common skin and nail problems. However, it is not known how these foot problems impact upon people’s lives. Therefore, we aimed to explore this using a qualitative approach. Method: Following ethical approval, 12 participants were recruited who had a diagnosis of SLE, current and/or past experience of foot problems and were over 18 years in age. Following consent, interviews were carried out with an interpretivist phenomenological approach to both data collection and analysis. Results: Seven themes provide insight into: foot problems and symptoms; the impact of these foot problems and symptoms on activities; disclosure and diagnosis of foot problems; treatment of foot problems and symptoms; perceived barriers to professional foot care; unanswered questions about feet and foot care; and identification of the need for professional foot care and foot care advice. Conclusion: These participants tend to “self-treat” rather than disclose that they may need professional foot care. A lack of focus upon foot health within a medical consultation is attributed to the participant’s belief that it is not within the doctor’s role, even though it is noted to contribute to reduced daily activity. There is a need for feet to be included as a part of patient monitoring and for foot health management to be made accessible for people with SLE

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab

OBJECTIVE: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. METHODS: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. RESULTS: All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. CONCLUSIONS: Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach