OBJECTIVES: Characteristics of Swiss patients with systemic sclerosis have not been described so far. The aim of the current study was to identify unmet needs in comparison with other European countries that could inform specific interventions to improve the care of systemic sclerosis patients. CONCLUSION: This is the first report of the national Swiss EUSTAR cohort. It identifies earlier referral to systemic sclerosis expert centres, before major organ damage occurs, and when outcome can still be modified, as a priority to improve care of patients with systemic sclerosis.
О р и г и н а л ь н ы е и с с л е д о в а н и я ФГБНУ «Научноисследовательский институт ревматологии им. В.А. Насоновой»,
BackgroundCyclophosphamide (CyP) is considered as a drug of choice for the treatment of interstitial lung disease (ILD) in the patients with systemic sclerosis (SSc). However, according to the literature, the use of CyP leads to rather limited and transient improvement of the pulmonary fibrosis. In this context the search for novel, more efficacious agents has been continued, such as attracting much attention retuximab (RTM).ObjectivesTo compare the impact of CyP and RTM on SSc clinical manifestation and activity, and the safety of these agents in the open-label prospective non-randomized study.Methods107 patients with the confirmed SSc diagnosis and ILD evidence based on HRCT findings were enrolled into the study. All patients received low-dose and moderate-dose prednisolone regimens. 36 patients (Group A) received parenteral CyP for 12±6 months at total dose 10.6±5 g (the average age 47±12 years, females 92%, SSc duration 5.0±4.8 years, diffused/localized forms 1.6/1). 71 patients (Group B) received RTM at total dose 1.43±0.66 g over the follow-up period 13.2±2 months (the average age 46±13 years, females 83%, SSc duration 5.6±4.4 years, diffused/localized forms 1.4/1); to 32 (45%) of them RTM was added to immunosupressants due to inadequate efficacy of the latter. The time courses FVC(%), modified skin count (mRss, points), activity index (EScSG, points), left ventricle ejection fraction (LVEF,%), mean pulmonary arterial pressure (EchoCG), and cardiac rhythm and conductivity disorders (ECG) were evaluated.ResultsIn Groups A and B the therapy was associated with significant decrease in mRss (p=0.009 and 0,001, respectively) and EScSG (p=0.000165 and 0.001, respectively). Increase in LVEF (61.8±7.3 и 63.6±7.3. p=0.02) was observed only in RTM-treated patients.Evaluation of FVC time course in Groups A and B revealed significant FVC increase (p= 0.034 and 0.000045, respectively), with median increment about 5%.In Group A FVC 10% FVC increase was found in the third of the patients thus exceeding respective parameter in Group B (p=0.2). The patient percentage with FVC decrease by ≥10% was similar in both groups.During the follow-up period no change of the other studied parameters was observed.The therapy was better tolerated in RTM-treated group: during RTM therapy adverse reactions emerged in significantly lower proportion of the patients (11/14%) compared with CyP-treated group (19/53%), p=0,0000.ParametersGroup AGroup BEScSG 1M ± SD 2.8±2*2.8±1.8*EScSG 2M ± SD 1.4±1.17*1.3±1.1*mRss 1M ± SD 11.2±9.8 *11.3±9.6 *mRss 2M ± SD 7.9±6.8. *8.0±6.6*FVC 1M ± SD 80.5±20.1* 77.3+20 *FVC 2M ± SD 85.9±20.5*82.6+21.*Δ FVC%5.4[-0.6; 12.3]5.3[0.1; 10.2]FVC increment by ≥10%, n/%11/3114/19.7FVC decrement by ≥10% n/%2/5.64/5.6Notes:in Parameters column 1 = before treatment, 2 = after treatment; M ± SD = mean value and standard deviation; * = significant difference between the vales measured before and after the treatmentConclusionBoth agents effectively alleviated skin induration and EScSG, and significantly improved FVC. However, C...
Background:A sound experience has been accumulated up to date with the use of rituximab (RTХ) for treatment of systemic sclerosis (SSc). Some studies reported improvement of skin fibrosis following treatment with RTХ, but long-term follow-ups are really few.Objectives:to evaluate the effect of RTХ on the manifestations of skin fibrosis in patients (pts) with SSc in the long-term follow-up.Methods:This prospective study included 71 pts aged 46 years (17-66) on average, 59 (83%) pts were females, mean disease duration was 5,6±4,4 years, and mean follow-up - 42 months (12-72) (mo). Diffuse SSc was established in 42 (59%) pts. All pts received glucocorticoids in low doses. 45% of pts were receiving immunosuppressants at study entry. The following parameters were evaluated: Rodnan skin score (mRSS), interdigital space(IDS) (the distance between the tips of 1 and 5 fingers at maximum extension), oral aperture (OAp) and activity index (EScSG-AI) over the periods: 12-18 mo, 24-30 mo, 36-42 mo, 48-54 mo and 60-72 mo after initiation of RTX therapy. The results are presented as: mean values, delta (Δ), median, upper and lower quartiles.Results:RTX therapy resulted in significant decrease of disease activity index, which statistically significantly correlated with decrease of mRSS - the main indicator of the severity of skin fibrosis (r=0,39;p=0,001). Changes in parameters by follow-up periods are presented in the Table 1.Table 1.Changes in clinical and instrumental parameters at RTX treatment (delta; median; lower quartile; upper quartile).Parameters12-18 mo (n=71)24-30 mo (n=55)36-42 mo (n=36)48-54 mo (n=24)60-72 mo (n=17)ΔmRSS3,32 [3.3; 0; 8]5,4 [3; 0; 10]5,1 [3,5; 0; 9]5,3 [3; 0; 10]7,3 [5; 1; 14]p=0,001p=0,001p=0,001p=0,001p=0,001ΔOAp, cm0,24 [0,1; 0; 0,5]0,26 [0,1; 0; 0,6]0,39 [0,2; 0; 0,8]0,31 [0.3; 0; 0,7]0,36 [0,2; 0; 0,8]p=0,0009p=0,0006p=0,004p=0,006p=0,009ΔActivity index (EScSG-AI)1,49 [1,5; 0; 2,5]1,64 [1,5; 0; 2,5]1,11 [1; 0; 2]2 [2; 1; 3]2,17 [2; 1,5; 2]p=0,001p=0,001p=0,0001p=0,0001p=0,0001Cumulative dose of RTX, g1,43±0,62,97±0,83,45±1,33,96±1,15,15±1,7Decreasing of mRSS statistically significantly correlated with increasing cumulative dose of RTX (r=0,29;p=0,01). Decreasing disease activity index correlated with increasing cumulative dose of RTX (r=-0,37; p=0,01). IDS improvement was documented at all assessment time periods, although statistically insignificant.Conclusion:The results of this study confirm reported positive effect of RTX on the reduction of skin fibrosis in SSc. Long-term follow-up demonstrated steadily decreasing skin fibrosis and improvement of microstomia with increasing oral aperture in parallel with a decrease of the disease activity index and increasing cumulative dose of RTX.Disclosure of Interests:None declared
The choice of drugs for the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SS) is currently very limited. Data from a number of studies show that rituximab (RTM) can improve lung function and reduce the severity of skin fibrosis in patients with SS.Objective: to evaluate the efficiency of RTM in a cohort of patients with SS-associated ILD after one-year follow-up. The indications for prescribing RTM were: 1) the inefficiency of standard therapy with glucocorticoids and immunosuppressants (ISs) or the impossibility of their use; 2) the early stage (first 3 years of the disease) with signs of poor prognosis, such as diffuse form, high skin scores (>14), male gender, rapid progression with a significant initial decline in forced vital capacity (FVC) and/or diffusion lung capacity (DLC), and a high anti-Scl-70 antibody positivity.Subjects and methods. The investigators selected a group of patients who had at least two assessment points at a 12-to-18 month interval (the mean follow-up period of 13±2 months) and took at least 1 g of RTM during this period. The investigation included 71 patients with a valid diagnosis of SS. Multi-slice spiral computed tomography (MSCT) revealed ILD in 90% of patients. The disease duration was 5.6±4.4 years. The presence of anti-Scl-70 antibodies was detected in 73% of patients. The mean cumulative dose of RTM was 1.43±0.6 g; 48 patients in Group 1 received ≤2 g of RTM (the mean dose, 1.1±0.1 g) and 23 patients in Group 2 took ≥2 g of RTM (mean dose, 2±0.6 g). Before starting treatment with RTM, all the patients received concomitant therapy with prednisone and 45% - with immunosuppressants.Results and discussion. The results assessed by a physician showed that good and moderate effects of the therapy were observed in 52 (73.2%) and 16 (22.6%) patients, respectively; no effect was seen in 3 (4.2%) patients. Overall, 95.8% of patients reported various degrees of improvement. There were significant changes as reductions in the disease activity index, skin scores, C-reactive protein and IgG levels, the number of patients with a high antinuclear antibody level, and the mean dose of prednisolone as well as increases in an oral aperture size, left ventricular ejection fraction, and 6-minute walk test scores. There were no changes in pulmonary artery systolic pressure and the HAQ DI. FVC increased from 77.35±19.9 to 82.6±20.7% (p=0.001). A minimal clinically significant increase in FVC ≥5% was noted in 41 (57.7%) people. The overall improvement in FVC (ΔFVC) reached 5.24%, while the changes were more significant in Group 2 (ΔFVC 8.98%) than in Group 1 (ΔFVC 3.75%; p=0.01). DLC remained stable, but there were significant group differences: ΔDLC was 3.75% in Group 2 and, conversely, decreased in Group 1 (1.6%; p=0005). The safety profile of the therapy was regarded as good and quite comparable with both the safety profile of ISs and the use of RTM in other trials. Infectious complications were recorded to be most common in 11 (15%) people. Of these, upper respiratory tract infections developed in 7 patients; plantar phlegmon occurred in one case; urinary tract infection and herpes zoster were detected in two and one cases, respectively.The results of this study confirm data from other studies that have demonstrated that RTM exerts a positive effect on SS-associated ILD. We were the first to show the association of positive changes in the measures of pulmonary function tests with the dose of RTM.
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