OBJECTIVE To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHODS Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). RE-SULTS Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19 + B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. CONCLUSION RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.

Background: Outcomes from studies employing nitisinone 10 mg and 2 mg in alkaptonuria were compared. Patients and methods: Sixty-nine patients in each of the nitisinone (10 mg daily) and controls of suitability of nitisinone in alkaptonuria 2 (SONIA 2), as well as 37 and 23 in nitisinone (2 mg daily) and control cohorts at the National Alkaptonuria Centre (NAC), respectively, were followed up for 4 years. Severity of alkaptonuria (AKU) was assessed by the AKU Severity Score Index (AKUSSI). 24-h urine homogentisic acid (uHGA 24 ), serum HGA (sHGA), serum tyrosine (sTYR) and serum nitisinone (sNIT) were also analysed at each time point. Dietetic support was used in the NAC, but not in SONIA 2. Safety outcomes were also compared. All statistical analyses were post hoc. Results:The slope of the AKUSSI was 0.55, 0.19, 0.30, and 0.06 per month in the control NAC, nitisinone NAC, control SONIA 2, and nitisinone SONIA 2 cohorts, respectively. The intersection of the slopes on the x-axis was À132, À411, À295, and À 1460 months, respectively. The control and nitisinone slope comparisons were statistically significant both in the NAC (p < 0.001) and the SONIA 2 (p < 0.001). Corneal keratopathy occurred in 3 and 10 patients in the NAC and SONIA 2, respectively. Discussion: The nitisinone 10 mg dose decreased disease progression more than the 2 mg dose although the incidence of corneal keratopathy was 14.5% and 4.9%, respectively. Conclusion: Nitisinone 10 mg decreased urine and serum HGA, increased serum tyrosine, and decreased disease progression more than 2 mg. Low-protein dietetic support may be needed to mitigate tyrosinaemia following nitisinone.

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438 Background: Neo-adjuvant chemotherapy Improves overall survival in patients with MIBC. Nintedanib is an orally available, potent, small molecule, triple kinase inhibitor with the potential to further benefit patient prognosis. Methods: NEO-BLADE was designed as a randomised, placebo controlled phase II study (n=120) to compare the addition of nintedanib (N) (150mg/200mg BD) to a combination of Gemcitabine (G) and Cisplatin (C). The study was powered (80%, alpha=15% [one sided]) to detect an improvement in the histological complete response rate of 20% (OR = 2.37). Results: 120 patients were recruited from 15 sites between 04/Dec/2014 and 03/Sep/2018 (22% Female) with 109 patients evaluable. Complete response (CR) rates ( by ITT) were 22/57 (38.6%) and 25/63 (39.7%) for patients treated with/without N. Pathological CR on ITT was 21/57 (36.8%) and 20/63 (31.74%); For pathological evaluable patients it was 21/41 (51. 22% ) and 20/45 ( 44.44%) respectively. Patients treated with N showed a benefit in terms of PFS and OS with 12 month PFS rates of 89.0% and 74.1% in the Nintedanib and Placebo group respectively. P= 0.038 and HR (CI) 0.479 (0.236, 0.976). OS at 12/24 months N 96.26%/ 88.87% while in Placebo group 82.83%,/69.36%. P=0.022, HR (CI) 0.389 (0.168, 0.902). Toxicity was reported in terms of grade 3 adverse events [12/63 (19%) Placebo, 23/57 (40%) N] and Serious Adverse Events [35/63 (56%) Placebo, 34/57 (53%) N]. In terms of thromboembolic events, this was observed in 16/57 (28%) of patients treated with N and 13/63 (21%) without N (P=0.461). Conclusions: The study failed to reach its primary endpoint in demonstrating an improvement in pathological response rate between N and Placebo when given alongside G and C. The trial met its secondary end point in improvement of progression free survival and over all survival at 12 months and 24 months. Safety data from this placebo -controlled study confirms triplets can be given safely. There are efficacy signals with improvement in PFS and OS and the regimen warrants further investigation in randomised phase III trial. Translational studies to assess bio markers of response are planned. Clinical trial information: 11977.