Table 2 Summary of Randomized controlled clinical trials in the systemic oral treatment of ocular complications of Sjögren’s syndrome
Ono, M., et al. (2004) | 60 patients Group i (20) Group ii (21) Group iii (19) | Oral Cevimeline 20 mg or 30 mg 3 times daily | i. Placebo ii. Cevimeline | 4 weeks | • Dry eye symptoms (VAS) • CFS • Rose Bengal test • Schirmer I • TBUT | Cevimeline 20 mg: Improvement in symptoms, Rose Bengal test, CFS, TBUT compared with placebo. | • No drop outs mentioned |
Petrone, D., et al. (2002) | 197 patients Group i (70) Group ii (65) Group iii (62) | Oral Cevimeline 15 mg or 30 mg 3 times daily | i. Placebo ii. Cevimeline | 12 weeks | • Dry eye symptoms (VAS) • Schirmer I | Cevimeline 30 mg: Improved in VAS (P = 0.045) and Schirmer (p = 0.043) | • Short study period |
Yoon, C. H., et al. (2016) | 26 patients Group i (11) Group ii (15) | Oral HCQ 300 mg daily | i. HCQ, ii. Placebo | 12 weeks | • OSDI • CFS • Schirmer I • TBUT | All outcomes are not significant between i and ii at 12 weeks. | • Small sample size • Short study period • Insufficient washout period |
Gottenberg, J. E., et al. (2014) | 120 patients Group i (56) Group ii (64) | Oral HCQ 400 mg daily | i. HCQ ii. Placebo | 48 weeks | • Dry eye symptoms (VAS) | No improvement in VAS between i and ii | • Short study period • Ocular outcome is too subjective • No drop outs mentioned |
Sankar, V., et al. (2004) | 28 patients Group i (14) Group ii (14) | Etanercept 25 mg twice weekly subcutaneous | i. Etanercept ii. Placebo | 12 weeks | • Dry eye symptoms (VAS) • LGS • Schirmer I | No difference in ocular outcomes between i and ii | • Short study period • Small sample size |
Tsifetaki, N., et al. (2003) | 85 patients Group i (29) Group ii (28) Group iii (28) | Oral pilocarpine 5 mg 2 times daily | i. Pilocarpine ii. Artificial tears iii. Inferior lacrimal puncta occlusion | 12 weeks | • Dry eye symptoms (VAS) • Rose Bengal stain • Schirmer I | i improved in symptoms and Rose Bengal stain (P < 0.05) compared with ii and iii | • Short study period • All female subjects |
Dogru, m., et al. (2007) | 10 patients Group i (3) Group ii (7) | Oral Lactoferrin 270 mg daily | i. Oral lactoferrin ii. Placebo | 1 month | • Dry eye symptoms (VAS) • Corneal sensitivity • Schirmer I • TBUT • Tear lipid thickness • Vital staining scores | Significant improvement with Corneal sensitivity, tear lipid thickness and TBUT after 1 month of treatment | • No masking of investigator • Small sample size • Short study period |
Seitsalo, H., et al. (2007) | 22 patients | Oral doxycycline 20 mg 2 times daily | i. Low dose doxycycline ii. Placebo | 10 weeks | • Dry eye symptoms (VAS) | No difference between i and ii in terms of VAS | • Small sample size • No objective signs reported • Cross-over study • All female subjects |
Pillemer, S. R., et al. (2004) | 23 patients Group i (10) Group ii (13) | Oral DHEA 200 mg daily | i. DHEA ii. Placebo | 24 weeks | • Dry eye symptoms (VAS) • Schirmer I • LGS | No differences between i and ii for dry eye symptoms or Schirmer I. | • Small sample size • Limited ocular outcome measurements |
Hu, W., et al. (2014) | 240 patients Group i (160) Group ii (80) | Oral ShengJinRunZaoYangXue granules 200 g daily | i. ShengJinRunZaoYangXue granules ii. Placebo | 6 weeks | • Dry eye symptoms (11 point-Numerical Rating Scale) • Schirmer I | Schirmer I improved in i (P = 0.03 for left eye, P = 0.02 for right eye) | • Only 1 objective ocular outcome • Short study period |
Aragona, P., et al. (2005) | 40 patients Group i (20) Group ii (20) | Oral Linoleic acid (omega-6 essential FA) 112 mg + γ-linolenic acid 15 mg daily | i. Omega 6 essential fatty acid ii. Placebo | 1 month | • Dry eye symptoms (0–3 scoring system) • CFS • Schirmer I • TBUT • PGE1 (ELISA) | Significantly less symptoms in i compared to ii, reduced CFS in i than ii | • Small sample size • Short study period |
Brown, S., et al. (2014) | 110 patients | Intravenous Rituximab 1000 mg | i. Rituximab ii. Placebo | 48 weeks | • Dry eye symptoms (VAS) • Schirmer I | No significance between i and ii for dry eye symptoms and Schirmer I | • Small sample size |
Devauchelle-Pensec, V., et al. (2012) | 122 patients | Intravenous Rituximab 1000 mg | i. Rituximab ii. Placebo | 24 weeks | • Dry eye symptoms (VAS) • Schirmer I | No significance between i and ii for dry eye symptoms and Schirmer I | • Small sample size |