Randomized Controlled Trial of Rituximab and Cost-Effectiveness Analysis in Treating Fatigue and Oral Dryness in Primary Sjogren's Syndrome

被引:204
作者
Bowman, Simon J. [1 ]
Everett, Colin C. [2 ]
O'Dwyer, John L. [2 ]
Emery, Paul [3 ]
Pitzalis, Costantino [4 ]
Ng, Wan-Fai [5 ]
Pease, Colin T. [3 ]
Price, Elizabeth J. [6 ]
Sutcliffe, Nurhan [7 ]
Gendi, Nagui S. T. [8 ]
Hall, Frances C. [9 ]
Ruddock, Sharon P. [2 ]
Fernandez, Catherine [2 ]
Reynolds, Catherine [2 ]
Hulme, Claire T. [2 ]
Davies, Kevin A. [10 ]
Edwards, Christopher J. [11 ]
Lanyon, Peter C. [12 ,13 ]
Moots, Robert J. [14 ]
Roussou, Euthalia [15 ]
Giles, Ian P. [16 ]
Sharples, Linda D. [17 ]
Bombardieri, Michele [4 ]
机构
[1] Univ Hosp Birmingham NHS Fdn Trust, Mindelsohn Way, Birmingham B15 2TH, W Midlands, England
[2] Univ Leeds, Leeds, W Yorkshire, England
[3] Chapel Allerton Hosp, Leeds, W Yorkshire, England
[4] Barts & London Queen Marys Sch Med & Dent, London, England
[5] Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England
[6] Great Western Hosp, Swindon, Wilts, England
[7] Royal London Hosp, London, England
[8] Basildon & Thurrock Univ Hosp, Basildon, Essex, England
[9] Univ Cambridge, Addenbrookes Hosp, Cambridge, England
[10] Univ Sussex, Brighton, E Sussex, England
[11] Univ Hosp Southampton, NIHR Wellcome Trust Clin Res Facil, Southampton, Hants, England
[12] Univ Nottingham, Nottingham, England
[13] Circle Nottingham, Nottingham NHS Treatment Ctr, Nottingham, England
[14] Aintree Univ Hosp NHS Fdn Trust, Liverpool, Merseyside, England
[15] Barking Havering & Redbridge Univ Hosp NHS Trust, King George Hosp, Romford, Essex, England
[16] Univ Coll London Hosp, London, England
[17] London Sch Hyg & Trop Med, London, England
关键词
DISEASE-ACTIVITY INDEX; DRY EYE SYMPTOMS; CLINICAL-TRIALS; DOUBLE-BLIND; DAMAGE INDEX; EFFICACY; MULTICENTER; PILOCARPINE; IMPROVEMENT; COHORT;
D O I
10.1002/art.40093
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Objective. To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjogren'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) Sjogren's Syndrome Patient Reported Index and EULAR Sjogren'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+ pound/-264.75 and 2,672+ pound/-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.
引用
收藏
页码:1440 / 1450
页数:11
相关论文
共 33 条
[31]
Sjogren's syndrome disease damage index and disease activity index - Scoring systems for the assessment of disease damage and disease activity in Sjogren's syndrome, derived from an analysis of a cohort of Italian patients [J].
Vitali, Claudio ;
Palombi, Gianluigi ;
Baldini, Chiara ;
Benucci, Maurizio ;
Bombardieri, Stefano ;
Covelli, Michele ;
Del Papa, Nicoletta ;
De Vita, Salvatore ;
Epis, Oscar ;
Franceschini, Franco ;
Gerli, Roberto ;
Govoni, Marcello ;
Bongi, Susanna Maddali ;
Maglione, Wanda ;
Migliaresi, Sergio ;
Montecucco, Carlomaurizio ;
Orefice, Maddalena ;
Priori, Roberta ;
Tavoni, Antonio ;
Valesini, Guido .
ARTHRITIS AND RHEUMATISM, 2007, 56 (07) :2223-2231
[32]
Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome -: A randomized, placebo-controlled, fixed-dose, multicenter trial [J].
Vivino, FB ;
Al-Hashimi, I ;
Khan, Z ;
LeVeque, FG ;
Salisbury, PL ;
Tran-Johnson, TK ;
Muscoplat, CC ;
Trivedi, M ;
Goldlust, B ;
Gallagher, SC .
ARCHIVES OF INTERNAL MEDICINE, 1999, 159 (02) :174-181
[33]
Multiple imputation using chained equations: Issues and guidance for practice [J].
White, Ian R. ;
Royston, Patrick ;
Wood, Angela M. .
STATISTICS IN MEDICINE, 2011, 30 (04) :377-399