Simon J Bowman1, Colin C Everett2, John L O'Dwyer2, Paul Emery3, Costantino Pitzalis4, Wan-Fai Ng5, Colin T Pease3, Elizabeth J Price6, Nurhan Sutcliffe7, Nagui S T Gendi8, Frances C Hall9, Sharon P Ruddock2, Catherine Fernandez2, Catherine Reynolds2, Claire T Hulme2, Kevin A Davies10, Christopher J Edwards11, Peter C Lanyon12, Robert J Moots13, Euthalia Roussou14, Ian P Giles15, Linda D Sharples16, Michele Bombardieri4. 1. University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 2. University of Leeds, Leeds, UK. 3. Chapel Allerton Hospital, Leeds, UK. 4. Barts and The London School of Medicine and Dentistry, London, UK. 5. University of Newcastle, Newcastle-upon-Tyne, UK. 6. Great Western Hospital, Swindon, UK. 7. Royal London Hospital (Mile End), London, UK. 8. Basildon and Thurrock University Hospital, Essex, UK. 9. University of Cambridge, Addenbrookes Hospital, Cambridge, UK. 10. University of Sussex, Brighton, UK. 11. NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK. 12. University of Nottingham and Circle Nottingham, Nottingham NHS Treatment Centre, Nottingham, UK. 13. Aintree University Hospital, Liverpool, UK. 14. King George Hospital, Barking Havering and Redbridge University Hospitals NHS Trust, Essex, UK. 15. University College London Hospital, London, UK. 16. London School of Hygiene and Tropical Medicine, London, UK.
Abstract
OBJECTIVE: To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS). METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro-positivepatients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness. RESULTS:All 133 patients who were randomized to receiveplacebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group). CONCLUSION: The results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population.
RCT Entities:
OBJECTIVE: To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS). METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro-positive patients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness. RESULTS: All 133 patients who were randomized to receive placebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group). CONCLUSION: The results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population.
Authors: Luiz A Gueiros; Katherine France; Rachael Posey; Jacqueline W Mays; Barbara Carey; Thomas P Sollecito; Jane Setterfield; Sook Bin Woo; Donna Culton; Aimee S Payne; Giovanni Lodi; Martin S Greenberg; Scott De Rossi Journal: Oral Dis Date: 2019-06 Impact factor: 3.511