Management of adults with diabetes on dialysis: Summary of recommendations of the Joint British Diabetes Societies guidelines 2022.

Diabetes is the commonest cause of end-stage kidney disease in many parts of the world, and many people on dialysis programmes live with diabetes. Such people are vulnerable to complications from their diabetes, and their care may be fragmented due to the many specialists involved. This updated guidance from the Joint British Diabetes Societies aims to review and update the 2016 guidance, with particular emphasis on glycaemic monitoring in the light of recent advances in this area. In addition, the guidance covers clinical issues related to the management of diabetes in people on peritoneal dialysis, along with acute complications such as hypoglycaemia and ketoacidosis, and chronic complications such as foot and eye disease.

Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation.

SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period.

Ofatumumab for B cell depletion in patients with systemic lupus erythematosus who are allergic to rituximab.

OBJECTIVE: B cell depletion, most commonly with rituximab, is an evolving therapeutic approach in SLE. Infusion reactions after rituximab are common, and may prevent re-treatment in patients who previously demonstrated beneficial response. We have used ofatumumab, a fully humanized anti-CD20 mAb, as an alternative B cell-depleting agent in patients with SLE who are rituximab-intolerant due to severe infusion reactions. METHODS: A single-centre retrospective case series of 16 patients were treated with ofatumumab for SLE between 2012 and 2015. RESULTS: Ofatumumab infusion was well tolerated in 14/16 patients, in whom the median age was 34 (range 19-55) and the median duration of SLE 9.2 years (0.6-28.5). The cohort was heavily pre-treated, with 50% having prior CYC exposure, and a median cumulative dose of prior rituximab 4 g (1-6). Twelve patients were treated for LN, one for extra-renal flare and one for remission maintenance. B cell-depletion was achieved in 12/14 patients, with comparable reconstitution kinetics to a previous cohort treated with rituximab at our centre, and was associated with improvements in serological markers of disease activity, including ANA, anti-dsDNA antibody and complement levels. Half of the patients with LN achieved renal remission by 6 months. Progressive disease that was unresponsive to augmented immunosuppression with CYC was seen in five patients. During long-term follow-up (median 28 months), five grade III infections were reported, and there were no malignancies or deaths. CONCLUSION: In this pre-treated cohort with long-standing SLE, ofatumumab was a well-tolerated, safe and effective alternative to rituximab for B cell-depletion therapy.

Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series.

OBJECTIVES: B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab is a fully humanized anti-CD20 mAb that has shown efficacy in the treatment of haematological malignancy and RA. The use of ofatumumab in the treatment of AAV has not previously been reported. METHODS: This study was based on a case series of eight patients who received ofatumumab, in conjunction with low-dose CYC and oral steroids, in the treatment of AAV. RESULTS: Eight patients received ofatumumab: seven for remission induction in active disease (three relapsing; four with new disease) and one for remission maintenance. B cell depletion was achieved in all patients by 1 month, and was sustained for at least 6 months. All patients with active disease achieved clinical remission (BVAS of zero, or BVAS ⩽5 if all scores due to persistent urinary abnormalities in the presence of stable or improving renal function) by 3 months. This was associated with a rapid fall in ANCA titres, reduced inflammatory responses and improvements in renal function. At 12 months, three patients had repopulated B cells associated with the recurrence of circulating ANCAs, although no patients experienced major clinical relapse in the first 24 months. No unexpected side effects were observed. CONCLUSION: Treatment with ofatumumab resulted in similar serological and clinical responses to those seen in previous cohorts treated at our centre with a comparable CS, CYC and rituximab-based regimen. Ofatumumab should be considered an alternative B cell depleting agent in patients who are intolerant of, or unresponsive to, rituximab.