Limits...
Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study.

Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Sirinian C, Karampetsou M, Yiannopoulos G, Andonopoulos AP - Rheumatology (Oxford) (2009)

Bottom Line: There was a significant increase of forced vital capacity (FVC) in the RTX group compared with baseline (mean +/- s.d.: 68.13 +/- 19.69 vs 75.63 +/- 19.73, at baseline vs 1-year, respectively, P = 0.0018).Similarly, diffusing capacity of carbon monoxide (DL(CO)) increased significantly in the RTX group compared with baseline (mean +/- s.d.: 52.25 +/- 20.71 vs 62 +/- 23.21, at baseline vs 1-year respectively, P = 0.017).To confirm our encouraging results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, 26504 Rion, Patras, Greece. jimdaoussis@hotmail.com

ABSTRACT

Objective: To assess the efficacy of rituximab (RTX) in SSc.

Methods: Fourteen patients with SSc were evaluated. Eight patients were randomized to receive two cycles of RTX at baseline and 24 weeks [each cycle consisted of four weekly RTX infusions (375 mg/m(2))] in addition to standard treatment, whereas six patients (control group) received standard treatment alone. Lung involvement was assessed by pulmonary function tests (PFTs) and chest high-resolution CT (HRCT). Skin involvement was assessed both clinically and histologically.

Results: There was a significant increase of forced vital capacity (FVC) in the RTX group compared with baseline (mean +/- s.d.: 68.13 +/- 19.69 vs 75.63 +/- 19.73, at baseline vs 1-year, respectively, P = 0.0018). The median percentage of improvement of FVC in the RTX group was 10.25%, whereas that of deterioration in the controls was 5.04% (P = 0.002). Similarly, diffusing capacity of carbon monoxide (DL(CO)) increased significantly in the RTX group compared with baseline (mean +/- s.d.: 52.25 +/- 20.71 vs 62 +/- 23.21, at baseline vs 1-year respectively, P = 0.017). The median percentage of improvement of DL(CO) in the RTX group was 19.46%, whereas that of deterioration in the control group was 7.5% (P = 0.023). Skin thickening, assessed with the Modified Rodnan Skin Score (MRSS), improved significantly in the RTX group compared with the baseline score (mean +/- s.d.: 13.5 +/- 6.84 vs 8.37 +/- 6.45 at baseline vs 1-year, respectively, P < 0.001).

Conclusion: Our results indicate that RTX may improve lung function in patients with SSc. To confirm our encouraging results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

Show MeSH

Related in: MedlinePlus

(A) Effects of RTX on skin infiltrating B cells. Numbers of infiltrating B cells in the dermis (y-axis) at baseline and at 24 weeks. The mean ± s.d. of infiltrating B cells was 5.41 ± 3.73 vs 2.70 ± 1.47 at week 0 vs week 24, respectively, P = 0.110 for the RTX group and 5.69 ± 2.16 vs 5.32 ± 1.36 at week 0 vs week 24, respectively, P = 0.54 for the control group. The arrows indicate patients with histological evidence of improvement of skin fibrosis. Apart from Patient 3, in all other patients improvement of skin histology is associated with RTX-induced decreases in the numbers of skin-infiltrating B cells. (B) Elimination of skin-infiltrating B cells of Patient 2 before (A) and following RTX (B) at 24 weeks.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2806066&req=5

Figure 4: (A) Effects of RTX on skin infiltrating B cells. Numbers of infiltrating B cells in the dermis (y-axis) at baseline and at 24 weeks. The mean ± s.d. of infiltrating B cells was 5.41 ± 3.73 vs 2.70 ± 1.47 at week 0 vs week 24, respectively, P = 0.110 for the RTX group and 5.69 ± 2.16 vs 5.32 ± 1.36 at week 0 vs week 24, respectively, P = 0.54 for the control group. The arrows indicate patients with histological evidence of improvement of skin fibrosis. Apart from Patient 3, in all other patients improvement of skin histology is associated with RTX-induced decreases in the numbers of skin-infiltrating B cells. (B) Elimination of skin-infiltrating B cells of Patient 2 before (A) and following RTX (B) at 24 weeks.

Mentions: The presence of T and B cells was assessed by immunohistochemistry in all biopsies. Representation of T cells was substantially limited in all patients; these were predominantly CD8+ T cells and no differences were observed at 24 weeks, compared with baseline (data not shown). The number of B cells was relatively low as well, but they were more abundant than T cells. RTX administration significantly reduced the number of B cells in three patients (Patients 2, 4 and 6) but had no effect on the remaining three patients of the RTX group (Patients 1, 3 and 5). Patients exhibiting B-cell depletion in the skin following RTX administration were the ones with the higher numbers of B cells at baseline. All three patients with skin B-cell depletion improved histologically. However, among the three non-B-cell depletors, there was a single patient who improved histologically (Patient 3). In the control group no difference was recorded in B cell numbers at 24 weeks compared with baseline. All data and representative skin immunohistochemistry are shown in Fig. 4.Fig. 4


Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study.

Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Sirinian C, Karampetsou M, Yiannopoulos G, Andonopoulos AP - Rheumatology (Oxford) (2009)

(A) Effects of RTX on skin infiltrating B cells. Numbers of infiltrating B cells in the dermis (y-axis) at baseline and at 24 weeks. The mean ± s.d. of infiltrating B cells was 5.41 ± 3.73 vs 2.70 ± 1.47 at week 0 vs week 24, respectively, P = 0.110 for the RTX group and 5.69 ± 2.16 vs 5.32 ± 1.36 at week 0 vs week 24, respectively, P = 0.54 for the control group. The arrows indicate patients with histological evidence of improvement of skin fibrosis. Apart from Patient 3, in all other patients improvement of skin histology is associated with RTX-induced decreases in the numbers of skin-infiltrating B cells. (B) Elimination of skin-infiltrating B cells of Patient 2 before (A) and following RTX (B) at 24 weeks.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806066&req=5

Figure 4: (A) Effects of RTX on skin infiltrating B cells. Numbers of infiltrating B cells in the dermis (y-axis) at baseline and at 24 weeks. The mean ± s.d. of infiltrating B cells was 5.41 ± 3.73 vs 2.70 ± 1.47 at week 0 vs week 24, respectively, P = 0.110 for the RTX group and 5.69 ± 2.16 vs 5.32 ± 1.36 at week 0 vs week 24, respectively, P = 0.54 for the control group. The arrows indicate patients with histological evidence of improvement of skin fibrosis. Apart from Patient 3, in all other patients improvement of skin histology is associated with RTX-induced decreases in the numbers of skin-infiltrating B cells. (B) Elimination of skin-infiltrating B cells of Patient 2 before (A) and following RTX (B) at 24 weeks.
Mentions: The presence of T and B cells was assessed by immunohistochemistry in all biopsies. Representation of T cells was substantially limited in all patients; these were predominantly CD8+ T cells and no differences were observed at 24 weeks, compared with baseline (data not shown). The number of B cells was relatively low as well, but they were more abundant than T cells. RTX administration significantly reduced the number of B cells in three patients (Patients 2, 4 and 6) but had no effect on the remaining three patients of the RTX group (Patients 1, 3 and 5). Patients exhibiting B-cell depletion in the skin following RTX administration were the ones with the higher numbers of B cells at baseline. All three patients with skin B-cell depletion improved histologically. However, among the three non-B-cell depletors, there was a single patient who improved histologically (Patient 3). In the control group no difference was recorded in B cell numbers at 24 weeks compared with baseline. All data and representative skin immunohistochemistry are shown in Fig. 4.Fig. 4

Bottom Line: There was a significant increase of forced vital capacity (FVC) in the RTX group compared with baseline (mean +/- s.d.: 68.13 +/- 19.69 vs 75.63 +/- 19.73, at baseline vs 1-year, respectively, P = 0.0018).Similarly, diffusing capacity of carbon monoxide (DL(CO)) increased significantly in the RTX group compared with baseline (mean +/- s.d.: 52.25 +/- 20.71 vs 62 +/- 23.21, at baseline vs 1-year respectively, P = 0.017).To confirm our encouraging results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, 26504 Rion, Patras, Greece. jimdaoussis@hotmail.com

ABSTRACT

Objective: To assess the efficacy of rituximab (RTX) in SSc.

Methods: Fourteen patients with SSc were evaluated. Eight patients were randomized to receive two cycles of RTX at baseline and 24 weeks [each cycle consisted of four weekly RTX infusions (375 mg/m(2))] in addition to standard treatment, whereas six patients (control group) received standard treatment alone. Lung involvement was assessed by pulmonary function tests (PFTs) and chest high-resolution CT (HRCT). Skin involvement was assessed both clinically and histologically.

Results: There was a significant increase of forced vital capacity (FVC) in the RTX group compared with baseline (mean +/- s.d.: 68.13 +/- 19.69 vs 75.63 +/- 19.73, at baseline vs 1-year, respectively, P = 0.0018). The median percentage of improvement of FVC in the RTX group was 10.25%, whereas that of deterioration in the controls was 5.04% (P = 0.002). Similarly, diffusing capacity of carbon monoxide (DL(CO)) increased significantly in the RTX group compared with baseline (mean +/- s.d.: 52.25 +/- 20.71 vs 62 +/- 23.21, at baseline vs 1-year respectively, P = 0.017). The median percentage of improvement of DL(CO) in the RTX group was 19.46%, whereas that of deterioration in the control group was 7.5% (P = 0.023). Skin thickening, assessed with the Modified Rodnan Skin Score (MRSS), improved significantly in the RTX group compared with the baseline score (mean +/- s.d.: 13.5 +/- 6.84 vs 8.37 +/- 6.45 at baseline vs 1-year, respectively, P < 0.001).

Conclusion: Our results indicate that RTX may improve lung function in patients with SSc. To confirm our encouraging results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

Show MeSH
Related in: MedlinePlus