Search results for: immunosuppressants

Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

Abstract:

Abstract Objectives. Rituximab (RTX) shown a positive effect in the treatment of systemic sclerosis (SSc). But there is still not enough data on comparing the effectiveness of RTX with immunosuppressants (IS). The aim of our study was to compare changes of lung function and skin score in SSc between two groups of patients (pts) - on RXT therapy (prescribed after ineffectiveness of previous therapy with IS) and on therapy with IS only. Methods. This study included 103 pts received RTX as an addition to previous therapy (group 1) and 65 pts received therapy with IS and prednisolone (group 2). The mean follow-up period was 12.6±10.7months. In group 1 the mean age was 47±12.9 years, female – 88 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. 82% pts had interstitial lung disease (ILD) and 92% were positive for ANA, 67% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.3±4.5 mg/day, IS at inclusion received 47% of them. The cumulative mean dose of RTX was 1.7±0.6 g. In group 2 the mean age was 50.8±13.8 years, female-53 pts (82%), the diffuse cutaneous subset of the disease had 44 pts (68%). The mean disease duration was 8.8±7.7 years. 81% pts had ILD and 88% were positive for ANA, 58% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 8.69±4.28 mg/day, IS received 57% of them. Cyclophosphamide (CP) received 45% of pts. The cumulative mean dose of CP was 10.2±15.1g. D-penicillamine received 30% of pts. Other pts was on mycophenolate mofetil or methotrexate therapy in single cases. The pts of the compared groups did not differ in the main demographic and clinical parameters. The results are presented as delta (Δ) - difference between the baseline parameter and follow up point. Results. In group 1 there was an improvement of all outcome parameters: increased of forced vital capacity, % predicted - ΔFVC=4% (p=0.0004); Diffusing capacity for carbon monoxide, % predicted remained stable (ΔDLCO=0.1%); improvement of the Rodnan skin score-ΔmRss=3.4 (p=0.001); decrease of Activity index (EScSG-AI) - ΔActivity index=1.7 (p=0.001). In group 2 the changes was insignificant: ΔFVC=-2.3%, ΔmRss=0.87, ΔActivity index=0.3. But there was a significant decrease of DLCO: ΔDLCO=-5.1% (p=0.001). Conclusion. The results of our study confirm the data on the positive effect of RTX in complex therapy in pts with SSc (decrease of skin induration, increase of FVC, stabilization of DLCO). Meantime, pts on IS and prednisolone therapy shown the worsening of lung function and insignificant changes of other clinical parameters. RTX could be considered as a more effective option in complex treatment of SSc in comparison with IS therapy

Keywords: immunosuppressants, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova

Abstract:

Objectives. Gastrointestinal involvement is one of the most common manifestations of systemic sclerosis (SSc). The aim of our study was to assess the frequency of gastrointestinal manifestations in SSc patients (pts) with interstitial lung disease (ILD) and their changes to rituximab (RTX) therapy. Methods. There were 103 pts with SSc in this study. The mean follow-up period was 12.6±10.7 months. The mean age was 47±12.9 years, females - 87 pts (84%), and the diffuse cutaneous subset of the disease 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had ILD and were positive for ANA. 67% of them were positive for anti-topoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, and immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. 90% of pts received omeprazole at a dose of 20-40 mg/day. Results. At inclusion, dysphagia was observed in 76 pts (74%), early satiety or vomiting in 32 pts (31%), and diarrhea in 20 pts (19%). We didn't observe any changes in gastrointestinal manifestation during RTX therapy. There was a decrease in the number of pts with dysphagia from 76 (74%) to 66 (64%), but it was insignificant. The number of pts with early satiety or vomiting and diarrhea didn't change. Conclusion. In our study, gastrointestinal involvement was observed in most of the pts with SSc-ILD. We didn't find any significant changes in gastrointestinal manifestations during RTX therapy. RXT does not worsen gastrointestinal manifestations in SSc-ILD.

Keywords: systemic sclerosis, dysphagia, rituximab, gastrointestinal manifestations

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

Abstract:

Objectives. There is very few data on changes of the musculoskeletal manifestations (artritis, arthralgia, muscle weakness, etc.) in systemic sclerosis (SSc) on rituximab (RTX) therapy. The aim of our study was to assess the severity of the musculoskeletal involvement in SSc patients (pts) and its changes during RTX therapy. Methods. Our study included 103 pts with SSc. The mean followup period was 12.6±10.7 months. The mean age was 47±12.9 years, female-87 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had interstitial lung disease (ILD) and were positive for ANA, 67% of them were positive for antitopoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. Arthritis was observed in 22 pts (21%), arthralgias in 47 pts (46%). Muscle weakness was observed in 17 pts (17%). Tendon friction rubs was established in 7 pts (7%). The results at baseline and at the end of the follow up are presented in the form of mean values. Results. There was an improvement of all outcome parameters and musculoskeletal manifestations on RTX therapy. There was a decrease in the number of pts with arthritis from 22 (21%) to 10 (9%), a decrease in the number of pts with arthralgias from 47 (46%) to 31 (30%). The number of pts with muscle weakness decreased from 17 (17%) to 7 (7%). The number of pts with tendon friction rubs decreased from 7 (7%) to 3 (3%). The creatine phosphokinase decreased from 365.5±186 to 70.8±50.4 (p=0.00006). The C-reactive protein (CRP) decreased from 23.2±31.3 to 8.62±7.4 (p=0.001). The dose of prednisolone was reduced from 11.3±4.5 to 9.8±3.5 mg/day (p=0.0004). Conclusion. In our study, musculoskeletal involvement was detected in almost half of the patients with SSc-ILD. There was an improvement of musculoskeletal manifestations despite a small cumulative dose of RTX. We also managed to reduce the dose of glucocorticosteroids. The improvement of musculoskeletal manifestations was accompanied by a decrease in laboratory parameters - creatine phosphokinase and CRP. RTX is effective option for treatment of musculoskeletal manifestations in SSc.

Keywords: arthritis, musculoskeletal involvement, systemic sclerosis, rituximab

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Authors: Saboor Saeed, Chunming Jiang

Abstract:

Eosinophilic Granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis of small and medium-sized vessels that primarily develops in middle-aged individuals. It is characterized by asthma, blood eosinophilia, and extra pulmonary manifestations. In childhood, EGPA is extremely rare. Pulmonary and cardiac involvement is predominant in pediatric EGPA, and mortality is substantial. Generally, EGPA will develop in three stages: a) The allergic phase is commonly associated with asthma, allergic rhinitis, and sinusitis, b) the eosinophilic phase, in which the main pathology is related to the infiltration of eosinophilic organs, i.e., lung, heart, and gastrointestinal system, c) vasculitis phase involved purpura, peripheral neuropathy, and some constitutional symptoms. The key to the treatment of EGPA lies in the early diagnosis of the disease. Early application of glucocorticoids and immunosuppressants can improve symptoms and the overall prognosis of EGPA. Case Description: We presented a case of an 8-year-old boy with a history of short asthma, marked eosinophilia, and multi-organ involvement. The extremely high eosinophil level in the blood (72.50%) prompted the examination of eosinophilic leukemia before EGPA diagnosis was made. Subsequently, this disease was successfully treated. This case report shows a typical case of CSS in childhood because of the extreme eosinophilia. It emphasizes the importance of EGPA is a life-threatening cause of children's eosinophilia. Conclusion: EGPA in children has unique clinical, imaging, and histological characteristics different from those of adults. In pediatric patients, the development and diagnosis of systemic symptoms are often delayed, mainly occurring in the eosinophilic phase, which will lead to specific manifestations. At the same time, we cannot detect a genetic relationship related to EGPA.

Keywords: Churg Strauss syndrome, asthma, vasculitis, hypereosinophilia, eosinophilic granulomatosis polyangiitis

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Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

Abstract:

Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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Authors: N. Garrós, P. Bustos, N. Beirampour, R. Mohammadi, M. Mallandrich, A.C. Calpena, H. Colom

Abstract:

Atopic dermatitis (AD) is a persistent skin condition characterized by chronic inflammation caused by an autoimmune response. It is a prevalent clinical issue that requires continual treatment to enhance the patient's quality of life. Systemic therapy often involves the use of glucocorticoids or immunosuppressants to manage symptoms. Our objective was to create and assess topical liposomal formulations containing Baricitinib (BNB), a reversible inhibitor of Janus-associated kinase (JAK), which is involved in various immune responses. These formulations were intended to address flare-ups and improve treatment outcomes for AD. We created three distinct liposomal formulations by combining different amounts of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), cholesterol (CHOL), and ceramide (CER): (i) pure POPC, (ii) POPC mixed with CHOL (at a ratio of 8:2, mol/mol), and (iii) POPC mixed with CHOL and CER (at a ratio of 3.6:2.4:4.0 mol/mol/mol). We conducted various tests to determine the formulations' skin tolerance, irritancy capacity, and their ability to cause erythema and edema on altered skin. We also assessed the transepidermal water loss (TEWL) and skin hydration of rabbits to evaluate the efficacy of the formulations. Histological analysis, the HET-CAM test, and the modified Draize test were all used in the evaluation process. The histological analysis revealed that liposome POPC and POPC:CHOL avoided any damage to the tissues structures. The HET-CAM test showed no irritation effect caused by any of the three liposomes, and the modified Draize test showed a good Draize score for erythema and edema. Liposome POPC effectively counteracted the impact of xylol on the skin, and no erythema or edema was observed during the study. TEWL values were constant for all the liposomes with similar values to the negative control (within the range 8 - 15 g/h·m2, which means a healthy value for rabbits), whereas the positive control showed a significant increase. The skin hydration values were constant and followed the trend of the negative control, while the positive control showed a steady increase during the tolerance study. In conclusion, the developed formulations containing BNB exhibited no harmful or irritating effects, they did not demonstrate any irritant potential in the HET-CAM test and liposomes POPC and POPC:CHOL did not cause any structural alteration according to the histological analysis. These positive findings suggest that additional research is necessary to evaluate the efficacy of these liposomal formulations in animal models of the disease, including mutant animals. Furthermore, before proceeding to clinical trials, biochemical investigations should be conducted to better understand the mechanisms of action involved in these formulations.

Keywords: baricitinib, HET-CAM test, histological study, JAK inhibitor, liposomes, modified draize test

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