P184 Developing a pathway for tocilizumab treatment in giant cell arteritis: a South London regional experience

Background Tocilizumab is now approved by the National Institute of Health and Care Excellence (NICE) for up to a year in relapsing or refractory giant cell arteritis (GCA). The practicalities of developing a pathway for referral using a hub and spoke model were previously unknown. Here we discuss our novel experiences utilising tocilizumab for GCA in its first year of licensing, after the introduction of a new regional multi-disciplinary team referral pathway. Methods We assessed all patients started on tocilizumab for GCA between August 2018-May 2019. The central assessing hub is St George’s University Hospitals NHS Foundation Trust, a large tertiary rheumatology department in the South of England, serving a population of 1.3 million. Results As per Table 1 below. A total of 9 patients were identified: 6 female and 3 male, with an average age of 74.2 (range 63-80). 5 patients were referred internally from clinicians at St George’s Hospital, with the remainder from local district general hospitals. Steroid protocols between patients were varied, and two-thirds required a 3-day IV methylprednisolone course, including all 4 patients with visual symptoms. A third of patients were on concurrent methotrexate, a disease-modifying antirheumatic drug. 8 of 9 patients were on alendronate, vitamin D/calcium, and a gastroprotective agent, and 7 were on aspirin. Reported side effects from steroids were common, with weight gain, increased appetite and osteoporosis noted. All our 9 patients continue their tocilizumab injections, with one individual having a 3-month break for a routine hip operation, and another a 1-month hiatus due to temporary derangement in liver function tests. Tocilizumab proffered improved disease control and few side effects were noted. 3 patients have now been on tocilizumab for 12 months and raise interesting discussions about ongoing funding and treatment efficacy. Conclusion Our case series shows the development and delivery of an effective hub and spoke referral pathway for tocilizumab treatment in GCA. We show that steroid dosing could be reduced with tocilizumab, and that all subjects received full funding for treatment. Our referral pathway has encouraged the uptake of the IL-6 monoclonal antibody treatment for GCA and compliance with NICE guidelines. Disclosures P. Saha None. V. Sandhu None. H. Robinson None. A. Ezeonyeji None. I. Al-Shakarchi None. S. Chander None. R. Suresh None. A. Kaul None. N. Sofat None.

Gastroprotective Effects of Plants Extracts on Gastric Mucosal Injury in Experimental Sprague-Dawley Rats

Rubus crataegifolius (black raspberry, RF), Ulmus macrocarpa (elm, UL), and Gardenia jasminoides (cape jasmine, GJ) are well known for hundreds of years as folk medicines in China and Korea to treat various gastrointestinal disturbance. The present study evaluated the gastroprotective effects of these plants either single or in combination against HCl/EtOH-induced gastritis and indomethacin-induced ulcer in rat model. Stomach ulcer was induced by oral ingestions of HCl/EtOH or indomethacin. Treatment with RF, UL, and GJ separately or in combination was done 1 h before ulcer induction. On HCl/EtOH-induced gastritis RF, UL, and GJ at a dose of 150 mg/kg showed comparable antigastritis effect (less than 50% inhibition) with lesion index of 94.97±8.05, 108.48±11.51, and 79.10±9.77 mm compared to cimetidine (45.33±23.73 mm). However, the combination of RF, UL, and GJ at a dose of 150 mg/kg with a ratio of 50:50:50 showed remarkable antigastritis effect with 77% inhibition. The observed lesion index at a ratio of 50:50:50 was 23.34±9.11 mm similar to cimetidine (18.88±19.88 mm). On indomethacin-induced ulcer, RF and GJ showed 38.28% and 51.8% inhibition whereas UL showed around 17.73% inhibition at 150 mg/kg. Combination of RF, UL, and GJ at 150 mg/kg showed strong antigastritis effect with 83.71% inhibition. These findings suggest strong gastroprotective effect of combined extract. In addition, these plants showed significant antioxidant activity in DPPH scavenging assay and antilipid peroxidation activity. Combination of black raspberry, elm, and cape jasmine might be a significant systemic gastroprotective agent that could be utilized for the treatment and/or protection of gastritis and gastric ulcer.

NEW FLAVONOID COMPOUND FROM ALLIUM HOOKERI THWAITES AS A GASTROPROTECTIVE AGENT

Objective: The main objective of this study was to investigate the antiulcer potential of an isolated flavonoid compound from Allium hookeri (AH).Methods: Oral administration of ethanol-induced ulcer to the mucosal layer of the stomach in the rats. The ulcer score and percentage protection was calculated from the stomach and gastric mucosal scrapping was carried out for the biochemical studies. Antioxidant study was carried out in liver and histopathological study of the ulcer stomach was performed.Results: Phytochemical investigation of methanolic extract of AH (MEAH) leaves afforded a new flavonoid compound characterized as 3, 5, 6-trihydroxy-2-(4-hydroxy-3-(6-hydroxy-4, 5, 6, 7-tetrahydro benzofuran-7-yl) phenyl-7-methoxy-4H-chromen-4-one (Compound 1). The flavonoid compound at the dose of 5 mg/kg showed a significant change in ulcer index by reducing the ulcer index and increased in percentage protection. It also increased the in vivo antioxidant activity by increasing the superoxide dismutase (SOD), glutathione (GLU) and catalase (CAT) levels. The isolated compound reversed the increase of mucin content in the mucosal scrapings. The histopathology study showed the reversed of normal gland texture in the mucous layer of the standard and compound 1 treated stomach when compared to the negative control.Conclusion: Present findings demonstrated the significant antiulcer activity and antioxidant activity of the isolated flavonoid compound as the supporting factor.

Design and Evaluation of Polyox and Pluronic Controlled Gastroretentive Delivery of Troxipide

Objective. Objective of the present work was to develop site-specific gastroretentive drug delivery of Troxipide using polymers Pluronic F127 and Polyox 205 WSR. Troxipide is a novel gastroprotective agent with antiulcer, anti-inflammatory, and mucus secreting properties with elimination half-life of 7.4 hrs. Troxipide inhibits H. pylori-derived urease. It is mainly absorbed from stomach. Methods. 32 factorial design was applied to study the effect of independent variable. Effects of concentration of polymer on dependant variables as swelling index, hardness, and % drug release were studied. Pluronic F127 and Polyox 205 WSR were used as rate controlled polymer. Sodium bicarbonate and citric acid were used as effervescent-generating agent. Results. From the factorial batches, it was observed that formulation F5 (19% Pluronic F127 and 80% Polyox 205 WSR) showed optimum controlled drug release (98.60% ± 1.82) for 10 hrs with ability to float >12 hrs. Optimized formulation characterized by FTIR and DSC studies confirmed no chemical interactions between drug and polymer. Gastroretention for 6 hrs for optimized formulations was confirmed by in vivo X-ray placebo study. Conclusion. Results demonstrated feasibility of Troxipide in the development of gastroretentive site-specific drug delivery.