Table 1

Summary-of-findings table generated for RCTs in primary-2002 patients with Sjögren syndrome

Author (year)No. patientsRoBArms (patients)Primary outcome (drug vs PLA arms, p value)Secondary outcomes (p value)SAEs (% of patients in each arm)InfectionsDeaths
Mariette et al (2004)12103LowINF (n=54) PLA (n=49)Improvement 30% joint pain, fatigue, dryness VAS at 22 w (20.4% vs 16.7%, p=0.62)Gammaglobulin (0.05), IgM (0.001)
Salivary flow rate, mL/min (p=0.24), Schirmer test (p=0.75), swollen joint count (p=0.75), tender joint count (p=0.97), ESR (p=0.97), CRP (p=0.96), IgA (p=0.56). Focus score (p=0.46).
INF (n=6) vs PLA (n=1)Not detailedNone
Dass et al (2008)1317Unclear comparative presentation of resultsRituximab (n=8), PLA (n=9)Improvement >20% VAS fatigue at 6 months (87% vs 56%, p=0.36)SF-36: social functioning (0.01)
NS: Immunoglobulin levels, titres or positivity for other antibodies, glandular manifestations of pSS, Schirmer-I test score, uSF rate.
RTX (n=2) vs PLA (n=0)Not detailedNone
Meijer et al (2010)1030Unclear (arms not balanced for baseline SF)Rituximab (n=20) PLA (n=10)Improvement of SWSF rate at 48 weeks (p>0.05)VAS oral dryness (p<0.05), VAS ocular dryness (p<0.05)Not classified as SAEsRTX 12 in 11 patients vs PLA 7 in 4 patientsNone
Norheim et al (2012)1426Moderate (27% men, required 2 phases separated 2 years)Anakinra (n=13), PLA (n=13)Group-wise comparison of fatigue scores at week 4 (p=0.19)Improvement >50% fatigue VAS (0.03)
NS W48: Lacrimal gland function, Schirmer’s test, mm/5 min, tear breakup time, seconds 3, 2; SF-36 total score, MFI, general fatigue.
W 24Raynaud’s phenomenon (p=0.057), tendomyalgia (p=0.074), arthralgia (p=0.058)
AKR (n=1) vs PLA (n=0)NoneNone
Devauchelle-Pensec et al (2014)15122LowRituximab 1 g/15 days (n=63), PLA (n=57)30 mm or greater improvement at week 24
on at least 2 of 4 VAS scores—dryness, fatigue, pain, global (23% vs 22%, p=0.91)
IgG (0.003), IgA (0.026), IgM (0.004)
ESSDAI score (p=0.60), systemic signs (p=0.089), salivary flow rate, mL/min (p=0.80), Schirmer test result, mm (p=0.054), ESR, mm/h (p=0.84), serum CRP level, mg/L (p=0.95), C4 complement level, g/L (p=0.32). B2-Microglobulin level, g/L (p=0.35), SF-36 score: PCS (p=0.36), MCS (p=0.35).
RTX 20.6% vs PLA 14%RTX 52.4% vs PLA 52.6%None
Gottenberg et al (2014)16120LowHCQ 400 mg/day (n=56) vs PLA (n=64)30% or greater reduction at week 24 in 2 of 3 VAS scores—dryness, fatigue, pain (17.6% vs 17.3%, p=0.96)ESR (<0.001), CRP (0.03), IgM (0.004)
ESSPRI (p=0.87), ESSDAI (p=0.63), cardinal signs (pain, fatigue, dryness) evaluated by practitioner (p=0.76), systemic signs evaluated by practitioner (p=0.49), SF-36, physical health component (p=0.85), SF-36, mental health component (p=0.23), HAD-anxiety (p=0.54), HAD-depression (p=0.26), Schirmer test (p=0.42), uSF, mL/min (p=0.45), serum IgG, g/L (p=0.13), serum IgA, g/L (p=0.85).
HCQ 3.6% vs PLA 4.7%NDPneumococcal meningitis (PLA group)
Ho Yoon et al (2016)1726High (primary outcome undefined)HCQ 300 mg/day (n=11), PLA (n=15)Not definedFluorescein staining score (p=0.524), Schirmer test score (p=0.958), OSDI (p=0.292), TBUT (p=0.746), ESR (p=0.620), serum IL-6 (p=0.991), serum and tear BAFF (NA), Th17 cells (p=0.566).Not classified as SAEsNoneNone
Bowman et al (2017)19133LowRituximab 1 g/15 days (n=67), PLA (n=66)Reduction ≥30% at week 48 of either fatigue or oral VAS dryness (39.3% vs 36.8%, p=0.76)uSF (0.0015)
ESSPRI (p=0.1087), ESSDAI scores (p=0.0721), mean lacrimal flow (p=0.3698), SF-36 physical component (p=0.5246), SF-36 mental component (p=0.9495).
PROFADSSI domains (p>0.05)
RTX n=9 vs PLA n=9RTX n=2 vs PLA n=2None
St Clair et al (2018)1852Unclear (study enrolment was terminated early because of expiration of study drug)BAM (n=33), PLA (n=19)Change in the SWSF rate at week 24 (+0.07 vs −0.01, p=0.33)Schirmer test right eye (0.036)
Unstimulated WSF (p=0.881), ESSDAI (p=0.104), physician global assessment (p=0.646), subject global assessment (p=0.587), overall dryness (p=0.744), fatigue (p=0.737), joint pain (p=0.797), Schirmer I test (mm)2 Left eye (p=0.662)
Total ocular staining score (p=0.603), SF-36: Physical aggregate score (p=0.163), Mental aggregate score (p=0.885). BAFF (pg/mL) (p=0.523), LIGHT (pg/mL) (p=0.840), IP-10 (pg/mL) (p=0.907)
BAM 15% vs PLA 5%BAM 24.2% vs PLA 15.8%None
  • AKR, anakinra; BAFF, B-Cell Activating Factor; BAM, baminercept ; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ESSDAI, EULAR Sjögren's syndrome disease activity index; ESSPRI, EULAR Sjogren's Syndrome Patient Reported Index; HAD, Hospital Anxiety and Depression Scale; HCQ, hydroxychloroquine; IL-6, interleukin 6; INF, infliximab; MCS, Mental Health Composite Score; MFI, Multidimensional Fatigue Inventory; ND, not detailed; NS, not significant; OSDI, Ocular Surface Disease Index; PCS, Physical Health Composite Score; PLA, placebo; PRO-FAD-SSI, Profile of Fatigue and Discomfort-Sicca Symptoms Inventory; pSS, primary Sjögren syndrome; RCT, randomised controlled trial; RoB, risk of bias; RTX, rituximab; SAEs, serious adverse events; SF-36, Short Form-36 Health Survey; SWSF, stimulated whole salivary flow; TBUT, Tear breakup time; uSF, unstimulated salivary flow; VAS, visual analogue scale; VAS, visual analogue scala; W, week; WSF, whole salivary flow.