Efficacy and safety of abatacept for patients with Sjögren's syndrome associated with rheumatoid arthritis: rheumatoid arthritis with orencia trial toward Sjögren's syndrome Endocrinopathy (ROSE) trial-an open-label, one-year, prospective study-Interim analysis of 32 patients for 24 weeks

Abstract

Abstract Objective. To assess the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). Methods. The primary endpoint of this 1-year, open-labeled, prospective, observational multicenter study of RA-associated secondary SS was the rate of SDAI remission at 52 weeks after initiation of abatacept therapy. The secondary endpoints included that of Saxson's test and Schirmer's test. Adverse events during the study period were also analyzed. Results. Thirty-two patients (all females) were enrolled in this study. Interim analysis at 24 weeks included assessment of efficacy (n = 31) and safety (n = 32). The mean SDAI decreased from 19.8 ± 11.0 (± SD) at baseline to 9.9 ± 9.9 at 24 weeks (P < 0.05). Patients with clinical remission, as assessed by SDAI, increased from 0 patient (0 week) to 8 patients (25.8%) at 24 weeks. Saliva volume (assessed by Saxson's test) increased slightly from 2232 ± 1908 (0 week) to 2424 ± 2004 (24 weeks) mg/2 min (n = 29). In 11 patients with Greenspan grading 1/2 of labial salivary glands biopsy, saliva volume increased from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min (P < 0.05). Schirmer's test for tear volume showed increase from 3.6 ± 4.6 (0 week) to 5.5 ± 7.1 (24 weeks) mm/5 min (n = 25; P < 0.05). Five adverse events occurred in five of 32 patients (15.6%), and three of these events were infections. Conclusion. Abatacept seems to be effective for both RA and RA-related secondary SS.

Keywords: Abatacept; Rheumatoid arthritis; Sjögren's syndrome.

Figure 1.

Effect of abatacept on RA. (A) Effects of abatacept treatment on Simplified Disease Activity Index (SDAI) in 31 patients. Data deficit was compensated by the last observation carried forward (LOCF) method (∗P < 0.05 vs. 0 week [baseline]), Wilcoxon signed-rank test. ABT, abatacept. (B) Effects of abatacept treatment on SDAI in 7 bio-switch patients and 24 bio-naïve patients. Data deficit compensated by the LOCF method (∗P < 0.05 vs. 0 week [baseline]), Wilcoxon signed-rank test. The difference between two groups was examined using Mann–Whitney U-test. ABT, abatacept; N.S, not significant. (C) Effects of abatacept and methotrexate combination treatment on SDAI in 23 patients and of abatacept alone in 8 patients. Data deficit was compensated by the LOCF method (∗P < 0.05 vs 0 week [baseline]), Wilcoxon signed-rank test. Difference between two groups was examined using Mann–Whitney U test. ABT, abatacept; N.S, not significant.

Figure 2.

Effect of abatacept treatment on RA disease activity. Effects of abatacept treatment on disease activity as assessed by SADI in 31 patients. Data deficit was compensated by the LOCF method. ABT, abatacept.

Figure 3.

Effect of abatacept on VAS in SS. (A) Effects of abatacept treatment on patients' VAS for dry mouth, dry eye, and parotid pain in 29 patients. Data deficit was compensated by the LOCF method (∗P < 0.05 vs 0 week [baseline]), Wilcoxon signed-rank test. VAS, visual analog scale; N.S, not significant. (B) Effects of abatacept treatment on physicians' VAS for dry mouth, keratoconjunctivitis sicca, and general condition in 28 patients. Data deficit was compensated by the LOCF method (∗P < 0.05 vs 0 week [baseline]), Wilcoxon signed-rank test. VAS, visual analog scale; KCS, keratoconjunctivitis sicca.

Figure 4.

Effects of abatacept on secretory function in SS. (A) Effects of abatacept treatment on saliva volume assessed by Saxson's test in 29 patients. Data deficit was compensated by the LOCF method. N.S, not significant vs. 0 week (baseline); Wilcoxon signed-rank test; ABT, abatacept. (B) Effect of abatacept treatment on saliva volume assessed by Saxson's test in 11 patients with Greenspan grading 1/2 of labial salivary gland (LSG) biopsy and in 16 patients with grade 3/4. Data deficit was compensated by the LOCF method (∗P < 0.05 vs 0 week [baseline]), Wilcoxon signed-rank test. Difference between two groups was examined using Mann–Whitney U test. ABT, abatacept; N.S, not significant. (C) Effects of abatacept treatment on tear volume assessed by Schirmer's test in 25 patients. Data deficit was compensated by the LOCF method (∗P < 0.05 vs. 0 week [baseline]), Wilcoxon signed-rank test. ABT, abatacept.

Figure 5.

Effect of abatacept on IgG, RF, and anti-SS-A antibody in SS. Effects of abatacept treatment on (A) serum IgG level (n = 31), (B) serum RF level (n = 30 patients), (C) titer of anti-SS-A antibody (n = 20 patients). Data deficit was compensated by the LOCF method (∗P < 0.05 vs 0 week [baseline]), N.S; not significant vs baseline, Wilcoxon signed-rank test. ABT; abatacept.

Figure 6.

Correlation between improvement in SS and RA. Correlation between (A) increase in saliva volume (assessed by Saxon's test) and fall in SDAI (n = 29 patients). Spearman's rank correlation coefficient = 0.211, not significant, and (B) between increase of tear volume (assessed by Schirmer's test) and fall in SDAI (n = 25 patients). Data deficit was compensated by the LOCF method. Spearman's rank correlation coefficient = 0.333, not significant.