FRI0324
IMMUNOSUPPRESSION FOR PRIMARY SJOGREN'S SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS
L. Chu1,*, K. Cui1, J. Pope1
1LHSC, London, Canada
Background: The current focus of treament in primary Sjogren’s Syndrome (pSS) is mainly symptom management. Since pSS is an autoimmune disease with multi-system involvement, there may be a role for systemic immunosuppression and/or biologic therapy. A wide variety of immune response targets have been examined in existing randomized controlled trials including inhibiting purine synthesis, blocking TNF-alpha, and depleting B lymphocytes. There is conflicting evidence as to whether immunomodulation alters disease progression.
Objectives: To assess the efficacy and safety of immunosuppressive therapy on pSS from clinical trials.
Methods: Five electronic databases (MEDLINE, EMBASE, CENTRAL, CLINICALTRIALS.GOV, WHO ICTRP) were searched to include randomized controlled trials of systemic immunosuppressive therapies in adults with pSS published in English prior to Oct 1, 2017. Efficacy measures included ocular dryness, oral dryness, fatigue, tear production, unstimulated and stimulated salivary flow, quality of life (QOL), ESSPRI, ESSDAI, ESR/CRP; Safety measures included serious adverse events (AEs) and withdrawals due to AEs.
Results: The searched yielded 32 trials evaluating 19 different medications. Studies enrolled anywhere between 7 to 133 patients, with the exception of 1 study with 497 patients. Mean age was in the fifth decade, with an average duration of diagnosis up to 9.2 years.
Twenty-two trials examined ocular and oral dryness, of which 2 and 3 revealed statistically significant improvements respectively (table 1). Only 1/14 trials found benefit for fatigue, none for tear production; 3/16 trials and 2/14 trials found increases in unstimulated and stimulated salivary flow respectively. Reductions in ESR were seen in 3/14 trials. Few studies examined QOL, ESSPRI, ESSDAI, and CRP. Trials often noted non-statistically significant trends toward improvement, but no particular drug or drug class consistently showed discrete benefit in subjective or objective efficacy measures possibly due to low statistical power.
Table 1: Efficacy Outcome Measures
Outcome |
# Trials Total |
# Trials showing statistical improvement |
|
Ocular dryness |
22 |
1 of 1 Prednisone 1 of 2 Rituximab |
|
Oral dryness |
22 |
1 of 3 Prednisone 1 of 3 Rituximab 1 of 3 DHEA |
|
Fatigue |
14 |
1 of 4 Rituximab |
|
Tear production |
19 |
0 |
|
Unstimulated saliva production |
16 |
2 of 3 Rituximab 1 of 3 Interferon alpha |
|
Stimulated saliva production |
14 |
2 of 4 Interferon alpha |
|
Quality of life (mental component) |
8 |
0 |
|
Quality of life (physical component) |
8 |
0 |
|
ESSPRI |
7 |
1 of 1 Iguratimod |
|
ESSDAI |
6 |
1 of 1 Baminercept |
|
ESR |
14 |
1 of 1 Nandrolone 1 of 1 Prednisone 1 of 3 Hydroxychloroquine |
|
CRP |
3 |
1 of 1 Hydroxychloroquine |
Meta-analyses of the above outcomes were performed at 6 months (Figure 1). With pooled estimates, significant improvements were seen in unstimulated salivary flow (p=0.003), stimulated salivary flow (p=0.02), and ESR (p<0.001). There was a trend towards increased serious AEs in the intervention groups, and a significant increase in withdrawals from AEs (RR 2.33, 95% CI 1.38 to 3.96).
Image/graph:
Conclusions: Reducing immune activity and inflammation potentially improves salivary gland function. Subjective measures may be less helpful as sicca symptoms likely have subtle progression if trials span less than 1 year. Given that most trials were small, beneficial treatment effects could be missed. Standardization of objective, reliable, clinically meaningful outcome measures that are sensitive to change may allow for positive treatments in the future.
Disclosure of Interest: None declared
DOI: 10.1136/annrheumdis-2018-eular.3008