ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 11L

Preliminary Results of a Double-Blind Randomised Trial of Rituximab Anti-B-Cell Therapy in Patients with Primary Sjogrens Syndrome

Simon Bowman1, Colin Everett2, Michele Bombardieri3, Robert Busch4, Paul Emery5, Frances Hall6, Colin T. Pease7, Costantino Pitzalis8, Elizabeth Price9, Luke Dawson10, Peter Smith11, Nurhan Sutcliffe3, Wan-Fai Ng12, Catherine Fernandez13, Sharon Ruddock13, Linda Sharples13, Catherine Reynolds13 and Sue Pavitt14, 1Rheumatology Dept, University Hospital Birmingham, Birmingham, United Kingdom, 2Leeds Institute for Clinical Trials Research, University of Leeds, LEEDS, United Kingdom, 3Experimental Medicine and Rheumatology, Queen Mary University of London, London, United Kingdom, 4Department of Life Sciences, University of Roehampton, London, United Kingdom, 5Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds Gen Infirmary, Leeds, United Kingdom, 6School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom, 7Rheumatology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, 8Centre for Experimental Medicine & Rheumatology, Queen Mary's School of Medicine and Dentistry, London, United Kingdom, 9Rheumatology Department, Great Western Hospital, Swindon, United Kingdom, 10School of Dental Sciences, University of Liverpool,, Liverpool, United Kingdom, 11School of Dental Sciences,, University of Liverpool, Liverpool, United Kingdom, 12NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, United Kingdom, 13Leeds Institute for Clinical Trials Research, University of Leeds, Leeds, United Kingdom, 14Division of Applied Health & Clinical Translation , School of Dentistry, University of Leeds, Leeds, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: October 27, 2015

Keywords: , ,

Session Information

Date: Tuesday, November 10, 2015

Title: ACR Late-breaking Abstract Poster Presentations

Session Type: ACR Late-breaking Abstract Session

Session Time: 9:00AM-11:00AM

Background/Purpose: Evidence from open-label and observational studies support anti-B-cell therapy in patients with primary Sjogren’s Syndrome (PSS). The TRACTISS trial aimed to determine the extent to which rituximab improves symptoms of fatigue and oral dryness in patients with PSS.

Methods: Multicentre, randomised, parallel group, double-blind, placebo-controlled trial. Patients with PSS, and symptomatic fatigue and oral dryness were recruited from 25 rheumatology clinics in the UK from June 2012 to January 2014. At weeks 0, 2, 24 and 26, patients received pre- and post-infusion corticosteroids and either placebo (P) IV or rituximab (R) IV (1000mg in 250mL). Intervention was decided by 24hr central telephone minimisation service. Primary endpoint was the proportion of patients achieving 30% reduction in either fatigue or oral dryness at 48 weeks, measured by Visual Analogue Scale (VAS). Other outcomes included VAS scales for fatigue or oral dryness separately, global assessment of PSS activity, pain, ocular and overall dryness, as well as salivary and lachrymal flow rates, quality of life, EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) and Patient Reported Index (ESSPRI). Patients and physicians were blinded to the patient’s allocation. ISRCTN 65360827

Results:

All patients (n=133) randomised to P (n=66) and to R (n=67) were included in the primary analysis. 55 P and 54 R patients received all 4 infusions in full. Mean age was 54 years, 93% of patients were female, mean ESSDAI was 5.7 and mean time since diagnosis was 5.7 years. Among complete cases at 48 weeks, 21/56 P and 24/61 R patients achieved the primary endpoint. After multiple imputation of missing outcomes, response rates were 36.8% (P) and 39.8% (R) (adjusted odds ratio 1.13, 95% confidence interval 0.50-2.55).  There were no significant differences in any outcome measure, except unstimulated salivary flow: P patients deteriorated compared to R patients with a significant relative difference seen after Week 24. There were more adverse events reported in total for R (275 P vs 325 R), but no difference in serious adverse events. (10 vs 10) One serious infusion reaction (R) and one serious anaphylaxis (P) occurred in one patient each.

Conclusion: TRACTISS is the largest randomised trial of biologic therapy in PSS. No improvement in symptoms was seen in the Rituximab arm (unlike the TEARS study) but modest benefit for Rituximab in salivary flow was observed.

Funding: Funded by Arthritis Research UK.

Table 1: Summary of results (* denotes values were log-transformed before analysis, and results back-transformed for presentation, ** denotes effects as a ratio, rather than a difference)

 

24 Weeks

48 Weeks

 

Placebo

Rituximab

Difference

Placebo

Rituximab

Difference

Unadjusted Complete Case analyses (95% Confidence Intervals)

Fatigue VAS Response rates (%)

30.5

(19.2, 43.9)

29.5

(18.5, 42.6)

-1.0

(-18.6, 17.0)

26.8

(15.8, 40.3)

29.5

(18.5, 42.6)

2.7

(-15.5, 20.7)

Oral Dryness VAS Response rates (%)

22.0

(12.3, 34.7)

21.3

(11.9, 33.7)

-0.7

(-18.6, 17.0)

17.9

(8.9, 30.4)

31.1

(19.9, 44.3)

13.3

(-4.9, 30.9)

Primary Endpoint (Either fatigue or oral dryness) response rates (%)

37.3

(25.0, 50.9)

34.4

(22.7, 47.7)

-2.9

(-20.2, 15.3)

37.5

(24.9, 51.5)

39.3

(27.1, 52.7)

1.8

(-16.3, 19.9)

Mixed Model Estimates – adjusted for baseline values (95% Confidence Intervals)

Fatigue VAS (0-100mm, 100=Severe)

64.5

(58.2, 71.5)

69.5

(63.7, 75.4)

4.7

(-2.9, 12.2)

65.8

(59.3, 72.2)

67.9

(61.3, 74.4)

2.1

(-5.9, 10.1)

Oral Dryness VAS (0-100mm, 100=Severe)

70.1

(63.9, 76.4)

70.2

(63.7, 76.7)

0.1

(-7.5, 7.6)

70.5

(64.5, 76.4)

66.4

(59.2, 73.7)

-4.1

(-12.0, 3.9)

Unstimulated Salivary Flow (mL/15min)*

0.66

(0.51, 0.87)

0.83

(0.64, 1.08)

1.25**

(0.91, 1.72)

0.59

(0.45, 0.77)

1.00

(0.76, 1.31)

1.71**

(1.23, 2.37)

ESSPRI (0-10, 10=Severe)

5.8

(5.3, 6.2)

6.3

(5.8, 6.8)

0.6

(0.01, 1.09)

5.7

(5.2, 6.2)

6.3

(5.7, 6.9)

0.5

(-0.1, 1.2)

ESSDAI (0-123, 123=Maximal activity)*

4.4

(3.6, 5.4)

4.1

(3.3, 5.2)

0.9**

(0.7, 1.2)

4.5

(3.5, 5.8)

3.4

(2.7, 4.4)

0.8**

(0.6, 1.0)

Disclosure: S. Bowman, Cellgene, 5,Glenmark, 5,GlaxoSmithKline, 5,Eli Lilly and Company, 5,Novartis Pharmaceutical Corporation, 5,Roche Pharmaceuticals, 5,Takeda, 5,UCB, 5; C. Everett, None; M. Bombardieri, None; R. Busch, None; P. Emery, Pfizer, MSD, AbbVie, UCB, Roche, Bristol-Myers Squibb, 5; F. Hall, None; C. T. Pease, None; C. Pitzalis, None; E. Price, None; L. Dawson, None; P. Smith, None; N. Sutcliffe, None; W. F. Ng, Sanofi-Aventis Pharmaceutical, 5; C. Fernandez, None; S. Ruddock, None; L. Sharples, None; C. Reynolds, None; S. Pavitt, None.

To cite this abstract in AMA style:

Bowman S, Everett C, Bombardieri M, Busch R, Emery P, Hall F, Pease CT, Pitzalis C, Price E, Dawson L, Smith P, Sutcliffe N, Ng WF, Fernandez C, Ruddock S, Sharples L, Reynolds C, Pavitt S. Preliminary Results of a Double-Blind Randomised Trial of Rituximab Anti-B-Cell Therapy in Patients with Primary Sjogrens Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/preliminary-results-of-a-double-blind-randomised-trial-of-rituximab-anti-b-cell-therapy-in-patients-with-primary-sjogrens-syndrome/. Accessed .

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