Table 1

Description of the nine randomised controlled trials used for the development of STAR and their classification by the expert panel

Drug, first author, yearnPrimary endpointVisit used to compute STARKey secondary endpointsClassification by experts
Abatacept (ASAP-III), van Nimwegen, 20208 80 Not met:
Change in ESSDAI at W24.
Adjusted mean difference between groups at W24: −1.3 (95% CI −4.1 to 1.6), p=0.385.		 W24 No difference:
ESSPRI, PhGA, PatGA, OSS scores; UWSF, TBUT, Schirmer’s test (average in both eyes), ocular and oral dryness NRS values; C3/C4 level at W24.
Significant improvement:
IgG: adjusted mean difference between groups at W24: −0.1 (95% CI −0.2 to −0.01), p=0.028.
RF: adjusted mean difference between groups at W24:
−13.8 (95% CI −20.7 to −6.0), p<0.0001.		Positive
(‘in between’).
Baminercept (BAMIN), St Clair, 201835 52 Not met:
Change in SWSF at W24.
Baseline-adjusted mean change between groups at W24: −0.01 mL/min TTT vs 0.07 PBO, p=0.33.		 W24 No difference:
Change from baseline in ESSDAI, PhGA, PatGA, OSS scores; UWSF, dryness and fatigue VAS, Schirmer’s test values.		Negative.
Hydroxychloroquine (JOQUER), Gottenberg, 201436 120 Not met:
30% reduction in 2 of 3 VAS (dryness, pain, fatigue) at W24.
Percentage of responders, between-group difference at W24: 17.9% TTT vs 17.2% PBO;
OR 1.01 (95% CI 0.37 to 2.78), p=0.98 (after multiple imputations).		 W24 No difference:
Change from baseline to W24 in ESSPRI, ESSDAI, PhGA scores; Schirmer’s test, UWSF values.		Negative.
Hydroxychloroquine and leflunomide (RepurpSS),
van der Heijden, 20206 		29 Met:
Change in ESSDAI at W24.
Baseline-adjusted mean between-group difference at W24: −4.35 points (95% CI −7.45 to −1.25), p=0.0078.		 W24 No difference:
ESSPRI, PatGA scores; NRS oral and ocular dryness, Schirmer’s test, and C3/C4 levels at W24.
Significant improvement:
PhGA: baseline-adjusted mean between-group difference at W24: effect size −15.2 (95% CI −29.96 to −1.08), p=0.036.
UWSF: baseline-adjusted mean between-group difference at W24: effect size: 10.57 (95% CI 2.21 to 18.93), p=0.014.
Serum IgG: baseline-adjusted mean between-group difference at W24: effect size −3.32 (95% CI −5.28 to −1.37), p=0.0013.
IgM-RF: baseline-adjusted mean between-group difference at W24: effect size: −0.59 (95% CI −1.06 to −0.12), p=0.017.		Positive.
Ianalumab (anti-BAFFR), Dörner, 201937 27 Not met:
Change in ESSDAI at W12 (combined as well as in individual dose groups).		 W24 Significant improvement:
ESSPRI (repeated measurement
model).
10 mg/kg group:
At W12: −1.55 points (95% CI 0.03 to 3.08).
At W24: −1.92 points (95% CI 0.33 to 3.52).
PatGA and PhGA.		Positive.
Iscalimab (anti-CD40),
Fisher, 20205 		Total=44; in cohort 2=32 Met for cohort 2 only (10 mg/kg intravenously):
Change in ESSDAI at W12.
Baseline-adjusted between-group difference at W12: −5.21 points (95% CI 0.96 to 9.46), p=0.0090, one-sided.		 W12In cohort 2 only:
Significant improvement:
PhGA: between-group difference at W12: −12.16 (2.38 to 21.94).
Non-significant improvement:
ESSPRI: between-group difference at W12: −0.95 (−0.50 to 2.41).
PatGA: between-group difference at W12: −8.14 (−10.39 to 26.67).
UWSF: between-group difference at W12: 0.04 mL/min (−0.03 to 0.10).
Schirmer’s test: between-group difference at W12: +8.06 mm (−1.37 to 17.50) for the left eye; +9.07 mm (−4.61 to 22.75) for the right eye.		Positive.
Rituximab (TRACTISS), Bowman, 201716 133 Not met:
30% reduction in fatigue or oral dryness at W48.
OR for RTX vs PBO=1.13 (95% CI 0.50 to 2.55), p=0.76.
Baseline-adjusted absolute difference in response rates at W48: OR for RTX vs PBO=1.7 (95% CI −16.5 to 19.1), p=0.84.		 W48 No difference:
ESSPRI, ESSDAI scores, oral and ocular VAS values at W48.
Significant improvement:
UWSF: between-group difference at W48: OR 1.71 (95% CI 1.23 to 2.37), p=0.0015.		Positive
(‘in between’).
Rituximab (TEARS)
Devauchelle-Pensec, 201415 		120 Not met:
30 mm improvement in at least 2 of 4 VAS (PatGA, pain, fatigue, dryness).
Percentage points between-group difference at W24: OR for RTX vs PBO: 1.0 (95% CI −16.7 to 18.7), p=0.91.		 W24 No difference:
ESSDAI score, PhGA, UWSF, Schirmer’s test values.
Significant improvement:
IgG level: between-group difference at W24: 1.2 g/L (95% CI 0.4 to 2.0), p=0.003.		Positive
(‘in between’).
Tocilizumab (ETAP),
Felten, 202010 		110 Not met:
Percentage of responders at W24 defined as (1) decrease of ≥3 points in ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI compared with enrolment and (3) absence of worsening in PhGA.
Percentage of responders: 54.2% TTT (41.3; 66.7%) vs 62.1% PBO (49.0; 74.1%),
OR 1.6 (95% CI 0.3 to 3.3).		 W12 No difference:
ESSDAI score at W24 and change from baseline, ESSPRI score at W24 and change from baseline, UWSF value.		Negative.

  • ASAP-III, Abatacept Sjögren Active Patients Phase III Study; BAFFR, B-cell activating factor receptor; BAMIN, Baminercept; ESSDAI, EULAR Sjögren's Syndrome Disease Activity Index; ESSPRI, EULAR Sjögren's Syndrome Patient Reported Index; ETAP, Efficacy of TocilizumAb in Primary Sjögren’s syndrome; EULAR, European Alliance of Associations for Rheumatology; JOQUER, Randomized Evaluation of Hydroxychloroquine in Primary Sjogren’s Syndrome; n, number of participants; NRS, numeric rating scale; OSS, ocular staining score; PatGA, patient global assessment; PBO, placebo; PhGA, physician global assessment; RepurpSS, Leflunomide–hydroxychloroquine combination therapy in patients with primary Sjögren's syndrome; RF, rheumatoid factor; RTX, rituximab; STAR, Sjögren’s Tool for Assessing Response; SWSF, Stimulated Whole Salivary Flow; TBUT, Tear Break Up Time; TEARS, Tolerance and EfficAcy of Rituximab in primary Sjögren syndrome; TRACTISS, TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome; TTT, treatment; UWSF, unstimulated whole salivary flow; VAS, Visual Analogue Scale; W, duration in weeks.