Background: At present no drug or combination of drugs are clearly effective as disease modifying therapy in systemic sclerosis (SSc). Previous data have pointed out the efficacy of cyclophosphamide (CYC) in the treatment of SSc patients with fibrosing alveolitis, especially in those who had showed altered aspecific inflammation parameters (1). Objectives: To test efficacy, safety, and effects on activation/damage cellular markers of low-dose intravenous CYC in the treatment of "active" SSc. Methods: Eight SSc patients (7 F, 1 M; aging from 17 to 66, median 46 years; 5 with lcSSc and 3 dcSSc; disease duration ranging from 1 to 12, median 7 years) were studied at baseline and after 6-month intravenous CYC treatment (500 mg pulses at week 0, 1, 2, 6, 10, 14, 18, 22) (2). The following circulating activation/damage cellular markers were evaluated: von Willebrand factor (vWF) (ELISA) and intercellular adhesion molecule 1 (ICAM-1) (ELISA) for endothelial cells; soluble interleukin 2 receptor (sIL-2R) (ELISA) for T lymphocytes; procollagen III aminopropeptide (PIIINP) (RIA) for fibroblasts. Besides, for each patient a total skin score was calculated and pulmonary function tests (PFTs) were performed. Results: After the 6-month CYC treatment, a significant reduction of TTS (10.6 ± 9.4 vs. 7.8 ± 8.4, p = 0.02) and a "freezing" of pulmonary function were noted. CYC treatment did not influence circulating levels of the cellular activation markers. Δs (differences between 6-month and baseline values), calculated for each marker, did not correlate with the respective changing of TSS and PFTs. No patient discontinued CYC treatment because of side effects. PIIINP (μg/L) ICAM-1 (ng/mL) vWF (%) sIL-2R (pg/mL) baseline 4.03 ± 0.98 360.2 ± 87.8 130.4 ± 56.3 1025 ± 296 6 month 4.13 ± 1.23 353.9 ± 89.8 123.6 ± 30.3 1005 ± 338 p > 0.05 > 0.05 > 0.05 > 0.05 Conclusion: Our results suggest an efficacy of low-dose intravenous CYC on cutaneous and lung involvement, detached by any influence on circulating markers previously reported as correlated to disease activity. This treatment appears to be a very safe approach. The ascertained validity of TSS as an outcome measure (3) in SSc prompt us to investigate, on a larger series and by a controlled trial, the effect of low-dose intravenous CYC in this condition.1. 1. Akesson A et al. Arthritis Rheum 1994, 37: 729-35;2. 2. Martin-Suarez I et al. Ann Rheum Dis 1997, 56: 481-7;3. 3. Steen VD, Medsger TA. Arthritis Rheum 2001, 44: 2828-35 1. 1. Akesson A et al. Arthritis Rheum 1994, 37: 729-35;2. 2. Martin-Suarez I et al. Ann Rheum Dis 1997, 56: 481-7;3. 3. Steen VD, Medsger TA. Arthritis Rheum 2001, 44: 2828-35
A PILOT STUDY ON LOW-DOSE INTRAVENOUS CICLOPHOSPHAMIDE IN SYSTEMIC SCLEROSIS: EFFICACY, SAFETY AND EFFECTS ON CELLULAR ACTIVATION MARKERS
CUOMO, Giovanna;ABBADESSA, Salvatore;VALENTINI, Gabriele
2002
Abstract
Background: At present no drug or combination of drugs are clearly effective as disease modifying therapy in systemic sclerosis (SSc). Previous data have pointed out the efficacy of cyclophosphamide (CYC) in the treatment of SSc patients with fibrosing alveolitis, especially in those who had showed altered aspecific inflammation parameters (1). Objectives: To test efficacy, safety, and effects on activation/damage cellular markers of low-dose intravenous CYC in the treatment of "active" SSc. Methods: Eight SSc patients (7 F, 1 M; aging from 17 to 66, median 46 years; 5 with lcSSc and 3 dcSSc; disease duration ranging from 1 to 12, median 7 years) were studied at baseline and after 6-month intravenous CYC treatment (500 mg pulses at week 0, 1, 2, 6, 10, 14, 18, 22) (2). The following circulating activation/damage cellular markers were evaluated: von Willebrand factor (vWF) (ELISA) and intercellular adhesion molecule 1 (ICAM-1) (ELISA) for endothelial cells; soluble interleukin 2 receptor (sIL-2R) (ELISA) for T lymphocytes; procollagen III aminopropeptide (PIIINP) (RIA) for fibroblasts. Besides, for each patient a total skin score was calculated and pulmonary function tests (PFTs) were performed. Results: After the 6-month CYC treatment, a significant reduction of TTS (10.6 ± 9.4 vs. 7.8 ± 8.4, p = 0.02) and a "freezing" of pulmonary function were noted. CYC treatment did not influence circulating levels of the cellular activation markers. Δs (differences between 6-month and baseline values), calculated for each marker, did not correlate with the respective changing of TSS and PFTs. No patient discontinued CYC treatment because of side effects. PIIINP (μg/L) ICAM-1 (ng/mL) vWF (%) sIL-2R (pg/mL) baseline 4.03 ± 0.98 360.2 ± 87.8 130.4 ± 56.3 1025 ± 296 6 month 4.13 ± 1.23 353.9 ± 89.8 123.6 ± 30.3 1005 ± 338 p > 0.05 > 0.05 > 0.05 > 0.05 Conclusion: Our results suggest an efficacy of low-dose intravenous CYC on cutaneous and lung involvement, detached by any influence on circulating markers previously reported as correlated to disease activity. This treatment appears to be a very safe approach. The ascertained validity of TSS as an outcome measure (3) in SSc prompt us to investigate, on a larger series and by a controlled trial, the effect of low-dose intravenous CYC in this condition.1. 1. Akesson A et al. Arthritis Rheum 1994, 37: 729-35;2. 2. Martin-Suarez I et al. Ann Rheum Dis 1997, 56: 481-7;3. 3. Steen VD, Medsger TA. Arthritis Rheum 2001, 44: 2828-35 1. 1. Akesson A et al. Arthritis Rheum 1994, 37: 729-35;2. 2. Martin-Suarez I et al. Ann Rheum Dis 1997, 56: 481-7;3. 3. Steen VD, Medsger TA. Arthritis Rheum 2001, 44: 2828-35I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
