Efficacy and safety of abatacept in active primary Sjögren’s syndrome: results of a phase III, randomised, placebo-controlled trial

ObjectivesTo evaluate efficacy and safety of abatacept in adults with active primary Sjögren’s syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial.MethodsEligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] ≥5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored.ResultsOf 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI −3.2 abatacept vs −3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified.ConclusionsAbatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity.

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OP0162 ABATACEPT TREATMENT FOR PATIENTS WITH EARLY ACTIVE PRIMARY SJÖGREN’S SYNDROME: OPEN-LABEL EXTENSION PHASE OF A RANDOMIZED CONTROLLED PHASE III TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4439 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 102.2-102

Author(s):

S. Arends ◽

J. F. Van Nimwegen ◽

E. Mossel ◽

G. S. Van Zuiden ◽

K. Delli ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Phase Iii ◽

List Type ◽

Research Support ◽

Open Label ◽

Open Label Extension ◽

Sjögren‘S Syndrome

Background:Abatacept (CTLA-4-Ig) targets the CD80/CD86:CD28 co-stimulatory pathway required for full T-cell activation and T-cell dependent activation of B-cells. The Abatacept Sjögren Active Patients phase III (ASAPIII) trial is a mono-center, investigator-initiated, placebo controlled study with an open-label extension phase (NCT02067910), which assessed the efficacy and safety of weekly subcutaneous abatacept (125mg) in patients with early active primary Sjögren’s syndrome (pSS). Previous analyses of the double blind phase showed no significant effect of abatacept treatment compared to placebo on the primary endpoint, difference in EULAR Sjögren’s syndrome disease activity index (ESSDAI) at week 24.1Objectives:To evaluate the efficacy and safety of extended (48 weeks) open label abatacept treatment in pSS patients.Methods:Included patients had biopsy-proven pSS, fulfilled the AECG and ACR-EULAR criteria, had disease duration ≤7 years (median 2 years), ESSDAI ≥5, and 89% were anti–SSA positive. All 40 patients who received abatacept (ABA) in week 0-24 were subsequently treated with abatacept from week 24-48. Of the 40 patients who received placebo (PLB) in week 0-24, 2 were lost to follow up, and 38 were treated with abatacept from week 24-48. Systemic disease activity (ESSDAI), patient reported symptoms (ESSPRI), serological outcomes (RF and IgG), ocular staining score (OSS) and unstimulated whole salivary flow (UWS) were assessed. We evaluated whether outcomes improved within treatment groups, from week 0 to subsequent visits and from week 24 to subsequent visits:1.Within ABA→ABA treated patients:a. Week 0-48 to assess overall efficacy.b. Week 24-48 to assess additional efficacy of long term treatment.2.Within PLB→ABA treated patients:a. Week 0-24 to assess whether a placebo effect occurred.b. Week 24-48 to assess short-term efficacy of open label ABA.GEE modeling was used to test significance of changes over time. Missing data were not imputed.Results:ESSDAI and ESSPRI were improved within ABA/ABA patients between week 0-48 with additional efficacy after week 24, and within PLB/ABA patients after switching to ABA. Significant decreases in ESSDAI and ESSPRI were also seen within PLB treated patients between week 0-24 (Figure 1). IgG and RF were improved within ABA/ABA patients between week 0-48 with additional efficacy after week 24, and within PLB/ABA patients after switching to ABA. OSS was improved within ABA/ABA treated patients between week 0-48. UWS only showed significant improvement in week 36 within ABA/ABA treated patients. No changes in IgG, RF, OSS or UWS were seen within PLB treated patients. No deaths occurred. One serious adverse event possibly related to intervention occurred during ABA treatment.Conclusion:ESSDAI and ESSPRI improved significantly during 48-week treatment with abatacept. Placebo treated patients also showed significant improvement in both indices and further improvement occurred after switching to abatacept. Biological activity was decreased by abatacept treatment. 48-week abatacept treatment improved OSS, and might improve UWS. Abatacept was well tolerated by pSS patients.References:[1]van Nimwegen et al. Lancet Rheumatol.Published online 31-01-2020Acknowledgments:This study was funded by Bristol-Myers Squibb. We thank all patients for participation in the ASAP-III trial.Disclosure of Interests:Suzanne Arends Grant/research support from: Grant/research support from Pfizer, Jolien F. van Nimwegen Consultant of: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Esther Mossel: None declared, Greetje S. van Zuiden Speakers bureau: Roche, Konstantina Delli: None declared, Alja J. Stel: None declared, Bert van der Vegt Consultant of: Advisory board member for Philips and Visiopharm., Erlin A. Haacke: None declared, Lisette Olie: None declared, Leoni Los: None declared, Gwenny M. Verstappen: None declared, Sarah A. Pringle: None declared, Fred K.L. Spijkervet: None declared, Frans G.M. Kroese Grant/research support from: Unrestricted grant from Bristol-Myers Squibb, Consultant of: Consultant for Bristol-Myers Squibb, Speakers bureau: Speaker for Bristol-Myers Squibb, Roche and Janssen-Cilag, Arjan Vissink: None declared, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant of: Consultant for Bristol-Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Speaker for Bristol-Myers Squibb and Novartis.

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Herbal formula SS-1 increases tear secretion for Sjögren’s syndrome (Preprint)

10.2196/preprints.25321 ◽

2020 ◽

Author(s):

Ching-Mao Chang ◽

Po-Chang Wu ◽

Jr-Rung Lin ◽

Yeong-Jian Jan Wu ◽

Shue-Fen Luo ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Controlled Trial ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Immunomodulatory Activity ◽

Herbal Formula ◽

Double Blind ◽

Therapeutic Benefits ◽

Sjögren‘S Syndrome

BACKGROUND Sjögren’s syndrome (SS) is an autoimmune inflammatory disease that primarily affects the exocrine glands, leading to glandular dysfunction. The hallmark symptoms of SS are dry eyes and mouth, compromising the quality of life of patients and decreasing their capacity to perform their daily activities. OBJECTIVE This study aims to evaluate the efficacy of the herbal formula SS-1 for its potential therapeutic benefits for patients with Sjögren’s syndrome. METHODS The bioactivity profile of SS-1 was determined using four different SS-1 concentrations across 12 human primary cell systems of the BioMAP profile. After that, a randomized, double-blind, crossover, placebo-controlled trial were performed including 57 patients treated with SS-1 for 28 weeks. RESULTS Biologically multiplexed activity profiling in cell-based models indicated that SS-1 exerted anti-proliferative activity in B cells and promoted anti-inflammatory and immunomodulatory activity. In clinical trial, the treatment of SS-1 revealed a significant improvement in both eyes by Schirmer’s test, which were increased by 3.42 mm (95% CI, 2.44–4.41 mm) and 3.45 mm (95% CI, 2.32–4.59 mm), respectively, and a significant reduction in artificial tear use, which was −1.38 times/day, 95% CI, −1.95 to −0.81 times/day,. Moreover, these results indicated that the increases in BAFF and BCMA levels were dampened by 53.20% (295.29 versus 555.02 pg/mL) and 58.33% (99.16 versus 169.99 pg/mL), respectively. CONCLUSIONS SS-1 treatment significantly inhibited B-cell maturation antigen. No serious drug-related adverse effects were observed. Oral SS-1 administration may be a complementary treatment for Sjögren’s syndrome. CLINICALTRIAL Clinicaltrials.gov: NCT02110446. Registered April 10, 2014

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Pilocarpine Hydrochloride for the Treatment of Xerostomia in Patients with Sjögren's Syndrome in Taiwan—A Double-blind, Placebo-controlled Trial

Journal of the Formosan Medical Association ◽

10.1016/s0929-6646(09)60266-7 ◽

2006 ◽

Vol 105 (10) ◽

pp. 796-803 ◽

Cited By ~ 27

Author(s):

Cheng-Han Wu ◽

Song-Chou Hsieh ◽

Kuang-Lun Lee ◽

Chia-Li Yu ◽

Ko-Jen Li ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Controlled Trial ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Double Blind ◽

Double Blind Placebo ◽

Sjögren‘S Syndrome

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European League Against Rheumatism Sjögren's Syndrome Disease Activity Index and European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index: A Complete Picture of Primary Sjögren's Syndrome Patients

Arthritis Care & Research ◽

10.1002/acr.21991 ◽

2013 ◽

Vol 65 (8) ◽

pp. 1358-1364 ◽

Cited By ~ 47

Author(s):

R. Seror ◽

J. E. Gottenberg ◽

V. Devauchelle-Pensec ◽

J. J. Dubost ◽

V. Le Guern ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Activity Index ◽

Disease Activity Index ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

European League Against Rheumatism ◽

Patient Reported ◽

European League ◽

Sjögren‘S Syndrome

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Patient-Reported Outcomes Including Fatigue in Primary Sjögren's Syndrome

Rheumatic Disease Clinics of North America ◽

10.1016/j.rdc.2008.08.010 ◽

2008 ◽

Vol 34 (4) ◽

pp. 949-962 ◽

Cited By ~ 18

Author(s):

Simon J. Bowman

Keyword(s):

Sjögren’S Syndrome ◽

Patient Reported Outcomes ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome ◽

Patient Reported ◽

Sjögren‘S Syndrome

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Sjögren’s syndrome—management

10.1093/med/9780199642489.003.0128_update_001 ◽

2014 ◽

Author(s):

Wan-Fai Ng ◽

Arjan Vissink ◽

Elke Theander ◽

Francisco Figueiredo

Keyword(s):

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Salivary Flow ◽

Patient Reported Outcome Measures ◽

Sjogren's Syndrome ◽

Classification Criteria ◽

Disease Assessment ◽

Patient Reported ◽

Sjögren‘S Syndrome

Management of Sjögren’s syndrome (SS) encompasses confirmation of diagnosis, disease assessment, and treatment of glandular and systemic manifestations including special situations such as pregnancy and SS-related lymphoma. The American European Consensus Group (AECG) classification criteria 2002 are the current gold standard for the diagnosis of SS. Salivary gland sialometry, sialochemistry, and ultrasound and tear osmolarity may be useful adjuncts. Recently, preliminary classification criteria of the American College of Rheumatology have been introduced as an alternative to the AECG criteria. Symptoms of SS are non-specific and must be actively explored. When assessing patients with SS, it is important to consider not only objective parameters such as abnormalities in blood tests and changes in tear and salivary flow, but also patient-reported outcome measures and impact on quality of life. Current management of patients with SS is hampered by the lack of evidence-based strategies. The symptoms experienced by patients with SS are often not fully appreciated by clinicians, which may contribute to the suboptimal management of the condition. Management of fatigue remains a major challenge and a holistic, multidisciplinary approach is recommended. Factors that may contribute to fatigue should be fully addressed. Recent advances in the understanding of the pathogenic mechanisms of SS have informed more targeted therapeutic strategies with some promising data. Optimal management of SS requires expertise from different disciplines. Combined clinics with rheumatology, oral medicine, and ophthalmology input will improve care and communications as well as reduce the number of clinic visits for patients and healthcare-related cost. Effective link between pSS specialists, dentists, opticians, and general practitioners will facilitate early diagnosis and reduce risk of long-term disability of SS.

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