Cyclosporine Group Research Articles

Cyclosporine Ameliorates Silica-Induced Autoimmune Hepatitis in Rat Model by Altering the Expression of Toll-Like Receptor-4, Interleukin-2, and Tumor Necrosis Factor-α.

Autoimmune hepatitis (AIH) is an inflammatory liver disease that is characterized histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by the presence of autoantibodies. Toll-like receptor (TLR)-4 is a TLR family member that, upon activation in hepatocytes, initiates a cascade of events. Interleukin-2 (IL-2) and tumour necrosis factor α (TNF-α) are potent inflammatory cytokines secreted in AIH, playing an important role in the early development of inflammation and hepatocyte damage. This study examined the role of cyclosporine in AIH and illustrated its actions on altered hepatic function in the silica-induced AIH model. AIH was induced in Wistar rats using sodium silicate. The rats were divided into four groups: the control group, silica-AIH group, cyclosporine-treated group, and prevention group. TLR-4 and IL-2 mRNA expressions in liver tissues were tested by RTPCR. AIH was associated with up-regulation of liver enzymes, IL-2 and TLR-4 gene expression, while cyclosporine significantly down-regulated the expression of both. The relative quantity of TLR-4 mRNA was 1±0, 13.57±1.91, 4±0.38, and 2±0 in control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Also, the relative quantity of IL-2 mRNA was 1±0, 14.79±1.42, 7.07±0.96, and 3.4±0.55 in control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Additionally, immunohistochemical staining for TNF-α in liver sections was increased in the silica-AIH group but was found to decrease in the cyclosporine-treated and prevention groups. This study advocates the therapeutic role of cyclosporine in treating immune-mediated hepatic diseases. Cyclosporine improves histological alterations in the liver and inhibits the production of proinflammatory cytokines.

The efficacy and safety of methotrexate and intermittent cyclosporine therapy in extensive chronic plaque psoriasis: A randomized, double-blind, and comparative study

Background: Psoriasis vulgaris is common papulosquamous disorder. Methotrexate (MTX) and cyclosporine, both of these drugs are in regular use for psoriasis management. But which one is superior in efficacy are yet to establish. Aims and Objectives: The aim of the study was to compare efficacy of MTX and intermittent cyclosporine therapy in the management of extensive/severe psoriasis, and to find and compare the incidence of adverse effects/safety of both the drugs. Materials and Methods: A randomized and controlled study was designed to compare the efficacy and safety of treatment. Patients with extensive psoriasis were randomly put in two groups –MTX and cyclosporine group and treated for 12 weeks. Results: Psoriasis area severity index (PASI) gradually reduced in both group, that is, up to second visit of study, (4 Weeks after induction of study) the reduction was at par. After that, it reduced in Cyclosporine group significantly faster than MTX group. At the end of the study, that is, after 12 weeks, the difference of PASI in both groups was not significant. Side-effects were not serious and minimal. Conclusion: Both the drugs are effective, but Cyclosporine is faster in onset than MTX. Adverse effects are nominal and not serious.

Prednisolone versus cyclosporine as initial treatment for Kawasaki disease.

Several studies have demonstrated the efficacy of prednisolone and cyclosporine as initial combination treatments for the prevention of coronary artery abnormalities (CAA) in patients with Kawasaki disease. However, whether prednisolone or cyclosporine results in superior clinical outcomes is unknown. Thus, this study aimed to compare the outcomes of these two treatments. Using the Japanese Diagnosis Procedure Combination database, we identified patients with Kawasaki disease who had received prednisolone or cyclosporine in addition to initial intravenous immunoglobulin treatment between April 2014 and March 2021. The primary outcome was the proportion of CAA; secondary outcomes included intravenous immunoglobulin resistance, medical costs, and length of hospital stay. Propensity score matching was conducted to compare outcomes between the two groups. We identified 6288 patients with Kawasaki disease who had received prednisolone (n = 6147) or cyclosporine (n = 141) as an initial treatment in combination with intravenous immunoglobulin. Four-to-one propensity score-matched analysis demonstrated no significant difference in the proportion of CAA (0.7% vs. 2.8%; p = 0.098), intravenous immunoglobulin resistance, or medical costs between the treatment groups. The length of hospital stay was significantly longer in the prednisolone group (14 vs. 11 days, p < 0.001). Prednisolone and cyclosporine used in the initial combination treatment for Kawasaki disease showed similar clinical outcomes regarding the risk of CAA, intravenous immunoglobulin resistance, and medical costs, whereas the length of hospital stay was longer in the prednisolone group than in the cyclosporine group.

Effectiveness of Corticosteroids Alone versus Corticosteroids and Cyclosporine in the Management of Patients with Severe Cutaneous Drug Reaction

Introduction: Severe Cutaneous Adverse Reactions (SCADRs) are emergency dermatologic manifestations associated with high morbidity and mortality. Their management includes immediate withdrawal of suspected causal agent followed by prompt management with drugs such as corticosteroids, cyclosporine and cyclophosphamide. Aim: To compare the effectiveness of corticosteroids alone versus cyclosporine and corticosteroids in management of SCADRs. Materials and Methods: This was a prospective observational study carried out in Indoor patients of Dermatology Department, Civil Hospital Ahmedabad, Gujarat, India, from October 2019 to September 2022. Twenty six patients were diagnosed with SCADRs and grouped according to the treatment received in two groups: corticosteroids alone (group B), and corticosteroids along with cyclosporine (group A). The efficacy was assessed based on: the days of disease arrest, days of complete reepithelialisation, duration of hospitalisation and final outcome. To know the prognosis of the patients, Score of Toxic Epidermal Necrosis (SCORTEN) score was used. Data was entered and analysed with the help of Microsoft excel ® 2019. Results: There were 14 patients in group A and 12 in group B. In a total 26 cases majority were of Stevens-Johnson Syndrome (SJS) (50%) followed by SJS-Toxic Epidermal Necrolysis (TEN) (27%) TEN (15%), Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) (8%). The mean duration of disease arrest was significantly shorter in group A (n=14) when compared to group B (n=12) (p-value &lt;0.001**). Also, the time for complete re-epithelisation was significantly shorter in group A than group B (p-value=0.025*) While no significant difference between the two groups was observed in SCORTEN score. Mortality was 3/12 in group B, nil in group A. Conclusion: Combination therapy with corticosteroids and cyclosporine leads to an early arrest of the disease progression, better prognosis and outcome in patients of SCADRs.

Enhanced Immunomodulation, Anti-Apoptosis, and Improved Tear Dynamics of (PEG)-BHD1028, a Novel Adiponectin Receptor Agonist Peptide, for Treating Dry Eye Disease

Dry eye disease (DED) is characterized by impaired tear dynamics, leading to complex pathophysiological conditions. (PEG)-BHD1028, a peptide agonist to AdipoRs, was evaluated as a potential therapeutic agent for DED based on the reported physiological function of adiponectin, including anti-inflammation and epithelial protection. Therapeutic effects of (PEG)-BHD1028 were evaluated in experimentally induced EDE with 0.001%, 0.01%, and 0.1% (PEG)-BHD1028 in mice and 0.1%, 0.2%, and 0.4% in rabbits for 10 days. In the rabbit study, 0.05% cyclosporine was also tested as a comparator. The results from the mouse study revealed significant improvement in tear volumes, tear breakup time (TBUT), inflammation, and corneal severity score (CSS) within 10 days at all (PEG)-BHD1028 concentrations. In the rabbit study, the tear volume and TBUT significantly increased in (PEG)-BHD1028 groups compared with vehicle and 0.05% cyclosporine groups. The CSS, apoptosis rate, and corneal thickness of all (PEG)-BHD1028 and 0.05% cyclosporine groups were significantly improved relative to the vehicle group. The immune cell counts of 0.2% and 0.4% (PEG)-BHD1028 treated groups were significantly lower than those of the vehicle group. These results represent the potential of (PEG)-BHD1028 as an effective therapeutic agent for DED.

Clinical efficacy of 0.05% cyclosporine nano-emulsion in the treatment of dry eye syndrome associated with meibomian gland dysfunction.

To evaluate the clinical efficacy of topical 0.05% cyclosporine nano-emulsion in the treatment of dry eye syndrome (DES) with meibomian gland dysfunction (MGD). This prospective study included 64 patients with DES and MGD who were randomly assigned to three groups: Group 1 (n=24, conventional cyclosporine), Group 2 (n=21, nano-emulsion cyclosporine), and Group 3 (n=19, control). Lid margin telangiectasia (LMT), meibomian gland secretion (MGS), conjunctival injection (CI), corneal staining (CS), tear break-up time (TBUT), Schirmer test I (STI), Ocular Surface Disease Index (OSDI), and lipid layer thickness (LLT) was evaluated at 4, 8, and 12wk of treatment. In Group 3 (control), LMT, CS, and CI improved after 8wk, MGS, TBUT after 12wk of treatment. In Group 1 (conventional cyclosporine), LMT, MGS, and TBUT improved significantly after 4wk, whereas CS, CI, STI, and LLT improved significantly after 8wk, and OSDI at 12wk. In Group 2 (nano-cyclosporine), LMT, MGS, CS, CI, TBUT, and OSDI significantly improved after 4wk, and STI after 8wk. Especially, LLT was significantly higher than other groups after 4wk. Cyclosporine and nano-cyclosporine shows significant improvement in DES with MGD than the control group. In contrast, the nano-cyclosporine group shows more statistically improved CI and CS at 4wk, especially LLT at 4, 8, and 12wk compared to the conventional cyclosporine group.

Topical cyclosporine versus allergen specific immunotherapy in perennial allergic conjunctivitis.

Symptom control in the long-term with less side effects is important in perennial allergic conjunctivitis, since would improve quality of life. This study aimed to assess the clinical efficacies of topical cyclosporin A and subcutaneous allergen immunotherapy (SCIT) in terms of sign control in perennial allergic conjunctivitis. This retrospective study included 20 adult patients with perennial allergic conjunctivitis and confirmed sensitization to house dust mites with skin prick test. Patients were assigned to either topical cyclosporine A treatment or SCIT. The participants were followed for 6months, and signs scores were recorded at 1, 3 and 6months. Overall, both cyclosporine and immunotherapy groups showed significant improvements in papillary reaction (p = 0.011 and 0.003, respectively), limbal involvement (p = 0.031 and 0.001), and conjunctival hyperemia (p = 0.001 and p < 0.001) scores during the 6-month follow-up. However, only cyclosporine group showed a significant improvement in corneal involvement scores (p = 0.015) during the study period. When scores at different time points were compared, significant improvement in conjunctival hyperemia was evident at 6months in both groups when compared to baseline (cyclosporine group, 0.7 ± 0.68 vs. 2.4 ± 0.84, 70.8% decrease, p = 0.01; immunotherapy group, 0.3 ± 0.48 vs. 2.3 ± 0.95, 87.0% decrease, p = 0.004), whereas for limbal involvement such an improvement was only evident in the immunotherapy group (0.1 ± 0.32 vs. 1.3 ± 0.95, 92.3% decrease, p = 0.01). Allergen immunotherapy and cyclosporin A treatment may provide effective sign relief in perennial allergic conjunctivitis. It may represent an encouraging treatment option particularly for cases with perennial allergic conjunctivitis refractive to other treatments and positive skin prick test to a specific allergen (house dust in the present study). Long-term relief by SCIT would reduce the side effects of polypharmacotherapy. Larger studies with longer follow-up are warranted to confirm our findings.

Clinical and laboratory parameters associated with treatment response to third-line therapies in chronic refractory urticaria: A real world study from northern India.

Current guidelines recommend omalizumab and cyclosporine for management of chronic spontaneous urticaria (CSU) refractory to anti-histamines. Identification of clinico-epidemiological characteristics predictive of treatment response with both modalities which will aid therapy selection. Clinical records of CSU patients receiving omalizumab and cyclosporine from May 1, 2016 to December 31, 2020 were reviewed retrospectively. Patients with a minimum follow-up duration of 4 months were included in the analysis. Treatment response was defined as >90% recorded reduction in Urticaria Activity Score-7 (UAS7) as compared to baseline 4 months after treatment initiation. Records of 1364 CSU patients were reviewed. A total of 56 patients who received omalizumab and 132 patients who received cyclosporine fulfilled the inclusion criteria. Treatment response was observed in 46 out of 56 (82.1%) patients in the omalizumab cohort and 106 out of 132 (80.3%) patients in the cyclosporine cohort (P=0.76). Factors significantly associated with response to omalizumab included high baseline serum IgE levels (P=0.028), lesser disease duration (P=0.001), and absence of prior immunosuppressant use (P=0.024). Factors predictive of cyclosporine response included high baseline UAS7 (P=0.048), low baseline IgE levels (P=0.047), and normal baseline D-dimer levels (P=0.027). Concomitant inducible urticaria, atopy, and angioedema were associated with non-response in both groups (P ≤ 0.05). Incidence of adverse events was slightly higher in cyclosporine group (28.7%) as compared to omalizumab group (19.5%, P=0.19). This study highlights several clinical parameters and laboratory markers that may be utilized to predict treatment response and aid in prognostication of patients with CSU.

Randomized controlled trial to compare safety and efficacy of mycophenolate vs. cyclosporine after rituximab in children with steroid-resistant nephrotic syndrome.

The comparative safety and efficacy of maintenance mycophenolate mofetil (MMF) and cyclosporine (CYC) following rituximab (RTX) in children with steroid-resistance nephrotic syndrome are uncertain. Multicenter randomized controlled trial. Sixty-six children between 2 and 6 years of age with SRNS. Patients were randomized to receive either MMF 1000 mg/m2 /day (n=32) or CYC 5mg/kg/day (n=34) for 12months following RTX induction therapy (375 mg/m2 ) given as needed for B-cell count. Complete remission and adverse events (AEs). Complete remission was observed in 26 patients (83.1%) in the MMF group compared with 21 patients (61.7%) in the CYC group (p=0.02). The median time to remission was shorter in the MMF group than in the CYC group (2.64 vs. 3.4 months; hazard ratio [HR], 0.61; 95% CI, 0.74-0.90, p=0.03). The median time to first relapse was longer in the MMF group compared with the CYC group (10.8 vs. 8.0 months; HR, 1.12; 95% CI, 1.31-1.54, p=0.01), and this was significantly correlated with the median time to B-cell recovery in the two groups (8.6 vs. 5.2 months in MMF and CYC, respectively, p=0.02). The overall incidence of adverse drug events was lower in the MMF group compared with the CYC group (59.3% vs. 76.4%, p=0.03). MMF-RTX is superior to CYC-RTX in maintaining remission with fewer AEs in children with initial SRNS. Additional high-quality randomized control trials with long-term follow-up are needed to identify the long-term potential complications.

Manifestations of vernal keratoconjunctivitis and comparison study of efficacy of different monotherapy with topical corticosteroid, cyclosporine and alcaftadine in its management in Sln Medical College, Odisha, India

Objective: The purpose was to study the ocular manifestations pattern and complications of vernal keratoconjunctivitis (VKC) and efficacy of corticosteroid, cyclosporine, alcaftadine. Material and methods: A Prospective study was done taking 227 patients from 15th Oct 2021 to 15th Mar 2022 in Department of Ophthalmology SLN Medical College and Hospital. Vernal Keratoconjunctivitis (VKC) was diagnosed basing on clinical presentation and scoring of signs and symptoms. Various investigations like slit-lamp biomicroscopy, keratometry, retinoscopy, distant direct, direct ophthalmoscopy and Corneal topography, fundus examination with +90D +20DVolk lenses done. Patients were allocated in 3 groups randomly for studying the efficacy of topical corticosteroid, cyclosporine and alcaftadine as monotherapy and first line therapy too. The results were analyzed after 4, 8 &amp; 12 weeks. Visual acuity and ocular complications were recorded. Results: Most common age group involved was 5 year to 9 year and least were more than of 20 years. Among the patients, 171 (75.4%) were male and 56 (24.6%) were female between 1-30 years. Most common presentation was limbal form. Complications like shield ulcer found in 11 and keratoconus in 2 patients. There was significant reduction in sign and symptom score in topical corticosteroid and topical cyclosporine group.

Combined use of cyclosporine in the treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis.

The exact efficacy of cyclosporine in the treatment of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) still needs evidence from more clinical data. This study was designed to compare the effectiveness and side-effects of combined use of cyclosporine in the treatment TEN with glucocorticoids (GC)/i.v. immunoglobulin G (IVIG). A total of 46 patients with SJS/TEN were enrolled and classified into two groups based on the therapeutic drugs used. Clinical characteristics, interventions, outcomes, and disease progressions were collected and compared between the two groups. In our cohort, seven patients eventually died and the overall fatality rate was 15.2%, but there was no difference between the two groups (p=0.557). On discharge, the median SCORe of Toxic Epidermal Necrosis (SCORTEN) fell from 2.0 at admission to 1.0 and the median body surface area detached fell from 32.0% at admission to 9.5%. Patients in the cyclosporine group had a higher rate of re-epithelialized area than patients in the non-cyclosporine group (p < 0.05). Cyclosporine significantly reduced the length of stay (19.0 vs. 13.0 days, p=0.019) and the rate of systemic infection (71.4% vs. 36.0%, p=0.017) compared with the non-cyclosporine group. SCORTEN was the only significant risk factor for death and the risk ratio was 1.96 (1.17-3.31, p=0.011). Conclusively, the combined use of cyclosporine could reduce the occurrence of systemic infection and accelerate the re-epithelialization.

Open-label Non-blinded Cohort study on Anti-Histaminic Resistant Chronic Idiopathic Urticaria in Western India.

Chronic idiopathic urticaria (CIU) is a chronic relapsing disease with hives for a period of six weeks or more. It has a significant impact on the physical and mental well-being of patients. Open-label non-blinded study of over 600 patients diagnosed with CIU was done. The aim of the study was to observe the following: 1. Characteristics of patients of anti-histaminic resistant CIU, 2. Efficacy of cyclosporin and any adverse events in the study population and 3. Prognosis and relapse rates of these patients at the end of one year. Detailed history taking and guided clinical evaluation were done to include chronic resistant urticarias in the study and their clinical characteristics and prognosis were studied. A total of 610 patients were diagnosed with CIU over a period of four years. Of these, 47 patients (7.7%) were diagnosed with anti-histaminic resistant urticaria. Of these, 30 patients (4.9%) who took treatment with cyclosporin at the above dosages were included in group 1. Rest 17 patients were in group 2 that were continued on anti-histaminics. Patients in cyclosporin group 1 showed a significant reduction in symptom scores as compared with group 2 at the end of six months. A lower need for corticosteroid therapy was noted in the cyclosporin group. Cyclosporin in low doses is very useful in anti-histaminic resistant urticaria with the duration of therapy being six months. It is cost-effective in low and medium-income countries and easily available.

The Effect of Systemic Methotrexate and Cyclosporine Combination Therapy inPsoriasis Vulgaris Patients in Bandung, Indonesia

Background: Methotrexate (MTX) and cyclosporine have been used as effective systemic mono-therapy for psoriasis. Several factors are considered to switch monotherapy to combination therapy because monotherapy is no longer effective and has higher side effects. Hence,clinicians have avoided systemic therapy combinations due to its toxicity. However, some studies showed that this combination therapy could be usedeffectively for psoriasis patients. Purpose: This study aimed to analyze the efficacy and adverse effects of systemic MTX and cyclosporine combination therapy in Indonesian psoriasis vulgaris patients. Methods: The retrospective study assessed the effectiveness of 3 monthsmono-therapyand combination therapy of systemic MTX and cyclosporine in psoriasisvulgaris patients from 2016–2017 in Dermatology Clinic, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. Result: Psoriasis area and severity index (PASI) score 90 were achieved in the group MTX (50%) and cyclosporine group (50%), while none in the combination group.However, eight patients (50%) in group MTX and cyclosporine reached the primary endpoint of PASI 50. One patient in cyclosporine group had adverse effects on kidney profiles. Nonetheless, other patients had no biochemical changes. But, there was no significant difference in the change of PASI between each group (p=0.102). Conclusion: We propose that combination therapy of MTX and cyclosporine is relatively safe and efficacious in treating Indonesian psoriasis vulgaris patients. This combination treatment isas effective as MTX or cyclosporinemono-therapy.

Experimental study of renal toxicity of cyclosporine and the ameliorative effect of N-acetylecysteine in albino rat

Introduction: Cyclosporine A (CsA) is considered powerful immunosuppressive drug which has improved the quality of life and survival rate of transplant patients and also used in autoimmune diseases. However, its use is limited by many side effects mainly nephrotoxicity. NAC is an antioxidant found to reduce CsA toxicity. Aim of the work: The study aims to determine the effect of exposure to cyclosporine on the kidney and to investigate the protective role of NAC. Methods: the study conducted on 50 adult male albino rats for 4 weeks, divided into 5 groups, group A the negative control group, group B the olive oil group (0.5 ml/d orally), group C the cyclosporine group (25mg/kg/d orally), group D the NAC group (600mg/kg/d orally) and group E the cyclosporine+NAC group. At the end of the study the evaluation was done by biochemical analysis and histopathology. Results: cyclosporine significantly affects the kidney by morphological changes in the form of dilatation of urinary space with congestion and lobulation of glomerullar capillaries in the renal corpusle. Proximal convoluted tubules showed degeneration of their cells with irregularity and destruction of brush border. Degeneration of distal convoluted tubules with exfoliation of some cells inside the lumen and the peritubular capillaries were congested and extravasated. Also cyclosporine affects the kidney by increasing serum urea and creatinine levels, while coadministration of NAC with cyclosporine attenuate its effects. Conclusion: cyclosporine causes renal injury through oxidative stress and NAC as an antioxidant attenuates but not fully protect against cyclosporine induced injuries.

Comparative effectiveness of various immunosuppressive therapy regimens for uveitis in patients with Behçet’s disease

The aim – to evaluate the effectiveness of various immunosuppressive therapy schemes for current uveitis used in real clinical practice in patients with Behçet’s disease (BD).Material and methods. The study included 531 patients with a reliable (ICBD criteria 2014) diagnosis of BD, observed in the V.A. Nasonova Research Institute of Rheumatology from 2006 to 2020. The majority were men (331 (62.3%)). The average age (M±SD) was 32.9±10.0 years, the median duration of BD (Me (25%; 75%)) – 96 (48; 174) months. 60.4% patients had uveitis, 70.7% – exacerbation of uveitis (EU). Uveitis activity was assessed by the BOS24 index (Behçet’s disease Ocular attack Score 24) in 202 patients with EU. The total activity of BD was evaluated according to BDCAF index (Behçet’s Disease Current Activity Form). Glucocorticoids (GC) was systematically received by 68.7% patients with EU, including 51.5% in the form of pulse therapy. 88.9% patients with EU received cytotoxics: 33.5% – cyclosporine (CS), 20.7% – azathioprine (AZA), 11.4% – AZA+COL, 8.8% – AZA+CS, 7.5% – colchicine (COL), 3.9% – cyclophosphamide (CPh). 11.9% patients with EU were prescribe Biologics, mainly i-TNF-α (11,4%: 8,8% – adalimumab, 2.2% – infliximab, 0.4% – golimumab) and rituximab (0.4%). The effectiveness of therapy was evaluated on average after 18.0 (8.0; 36.0) months.Results. According to the dynamics of BDCAF, by the end of follow-up, BD activity significantly decreased in all groups, with the exception of patients who received COL. A more significant decrease in BDCAF was observed in the combination therapy groups: AZA+CS (ΔBDCAF=–4.08±3.60), AZA+COL (ΔBDCAF=–3.57±2.50), as well as in the CS group (ΔBDCAF=–3.57±3.39), but no statistically significant differences in ΔBDCAF between the groups were obtained, which does not allow us to speak about a significant advantage of a particular drug. There were no significant differences in ΔBDCAF between patients who received (ΔBDCAF=–3.41±3.89) and those who did not receive (ΔBDCAF=–3.59±3.23) Biologics. According to the dynamics of BOS24, the most effective for relieving symptoms of intraocular inflammation were CS (ΔBOS24=–7.0 (–12.0; –3.0)), AZA (ΔBOS24=–7.0 (–15.0; –2.0)), a combination of CS+AZA (ΔBOS24=–5.0 (–8.0; –2.0)) and CPh (ΔBOS24=–4.0 (–14.0; –2.0). The differences between BOS24 before and after treatment in these groups were statistically significant. When assigning AZA+COL (ΔBOS24=–1.0 (–4.0; 0)) or COL (ΔBOS24=–0.5 (–2.0; 0)) uveitis activity decreased during therapy, but not significantly. According to ΔBOS24, uveitis therapy by CS was statistically significantly more effective compared to AZA+COL and COL; and AZA treatment, compared to COL. Biologics, mainly adalimumab, significantly and rapidly reduce the severity of intraocular inflammation (ΔBOS24=–7.0 (–18.0; 0)) compared with GC and cytotoxics (ΔBOS24=–4,0 (–9,0; –1,0)), however statistically significant differences between the groups were not obtained due to the small number of Biologics groups.Conclusion. CS, AZA and their combination, as well as i-TNF-α (mainly adalimumab) are more effective for relieving uveitis symptoms in patients with BD. BOS24 is a reliable tool for quantifying the activity of uveitis in BD patients and its dynamics against the background of anti-inflammatory and immunosuppressive therapy.

Infliximab is more effective than cyclosporine as a rescue therapy for acute severe ulcerative colitis: a retrospective single-center study.

BackgroundAcute severe ulcerative colitis (ASUC) is a potentially life-threatening disease, and the best option in cases of steroid-refractory disease is still debated. We compared the early- and long-term efficacy and safety of the 2 available “rescue therapies”, infliximab (IFX) and cyclosporine (CYS), in this setting.MethodsWe retrospectively evaluated patients admitted for ASUC and treated with “rescue therapy”. The primary endpoint was early colectomy-free survival (30 days) and colectomy-free survival until the end of follow up. The secondary endpoints were predictors of colectomy and long-term maintenance of the treatment strategy over time.ResultsOf 129 patients admitted, 68 received rescue therapy (47 with IFX), whereas 7 underwent early colectomy (10.3%). At 30 days, fewer patients treated with IFX showed a need for colectomy (8.5% vs. 14.3%) compared to those in the CYS group, though the difference was non-significant (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.10-4.69; P=0.47). No severe side effects due to IFX and CYS were observed. During a mean follow up of 40 months, 23 additional patients (37.7%) underwent colectomy, and the rate was significantly lower in the IFX group (25.6%) than in the CYS group (66.7%) (hazard ratio 0.25, 95%CI 0.10-0.61; P=0.003). Colectomy-free survival was significantly higher in the IFX group than in the CYS group (P=0.018) at 12 months.ConclusionsIn our setting, the early outcomes of IFX and CYS for ASUC were comparable. IFX was associated with significantly lower colectomy rates during the observation period and had a similar safety profile to CYS.

The ameliorative effect of N-acetylecysteine on cyclosporine induced testicular toxicity in male albino rats

Introduction: Cyclosporine A (CsA) is considered one of the potent drugs that are used extensively in organ transplant and oncology patients. It is also used in autoimmune diseases. Unfortunately, its use is accompanied with several hazards; one of these is testicular toxicity. Nacetylecysteine (NAC) is an antioxidant found to reduce CsA toxicity. Aim of the work: The study aims to determine the toxic effect of exposure to cyclosporine on the testis and to investigate the protective role of NAC. Methods: The study conducted on 50 adult male albino rats for 4 weeks divided into 5 groups, group A the negative control group, group B the olive oil group (0.5 ml/d orally), group C the cyclosporine group (25mg/kg/d orally), group D the NAC group (600mg/kg/d orally) and group E the cyclosporine+NAC group. At the end of the study the evaluation was achieved by biochemical analysis and histopathology. Results: Cyclosporine significantly affects the testis morphologically and functionally. The morphological changes are in the form of degenerative changes in the tubules with dislocation of germ cells into the lumen and irregular outlines, Congestion of blood capillaries in the interstitial tissue, and functionally the cyclosporine cause significant decrease in serum testosterone level. While co-administration of NAC with cyclosporine attenuate these effects. Conclusion: Cyclosporine causes testicular injury through oxidative stress and NAC as an antioxidant attenuates but not fully protect against cyclosporine induced testicular toxicity.

Пролонгированное применение селективных иммунодепрессантов в дренажной хирургии глаукомы: экспериментальное исследование in vivo

Background: anti-inflammatory and antiproliferative agents are among tools to prevent postoperative scarring. Prolonged use of immunosuppressants characterized by a selective mechanism of action immediately at the surgical site. Aim: to assess the safety and efficacy of bio-resorptive drainage devices enriched with cyclosporine or everolimus in vivo. Patients and Methods: the study was conducted on 52 rabbit eyes. Before to the study, ocular surface disease provoked by the long-term use of preservative-containing IOP-lowering medications was simulated. The next step was the penetrating surgical procedure. The surgery involved implanting bio-resorptive drainage devices of polylactide enriched with cyclosporine or everolimus or control devices (neither cyclosporine nor everolimus). Postoperatively, all rabbits underwent regular ophthalmic exams and IOP measurements. Follow-up was 6 months. After 7 days, 1 month, and 6 months, the animals were slaughtered for the histology of surgical site. Results: better characteristics of filtering blebs and lower IOP values were seen among the animals who underwent surgical procedures with immunosuppressants compared to the control group even in the early post-op period. After 1 month, control filtering blebs stopped functioning and were characterized by the IBAGS H0 (height) and E0 (extent) in most animals. Meanwhile, in cyclosporine and everolimus groups, filtering blebs were characterized by the IBAGS Н1-Н2 and Е1-Е3 till the end of follow-up. After 6 months, mean IOP was 17.3±0.5 mm Hg in the control group and 13.0±0.4 mm Hg and 11.8±0.6 mm Hg in cyclosporine group and everolimus group, respectively. No significant differences between the groups were reported in terms of complications. Histology matched clinical data and illustrated the mechanism of increased outflow facility after the implantation of drainage devices enriched with immunosuppressants. Conclusion: in vivo experiment has demonstrated higher efficacy and similar safety of IOP-lowering surgery after the implantation of drainage devices enriched with selective immunosuppressants. Keywords: glaucoma surgery, immunosuppressants, cyclosporine, everolimus, drainage device, scarring, filtering bleb. For citation: Germanova V.N., Karlova E.V., Volova L.T. et al. Prolonged use of selective immunosuppressants in glacoma drainage surgery: experimental in vivo study. Russian Journal of Clinical Ophthalmology. 2021;21(2):78–85. DOI: 10.32364/2311-7729-2021-21-2-78-85.

Comparison of serum monocide chemoattractant protein levels with immunosuppressive therapy protocols in patients with renal transplantation.

Renal transplantation stands out with lower cost advantages in life expectancy, quality of life and especially in the long-term perspective compared to dialysis. Having significant side effects of immunosuppressive drugs in terms of patient and graft survival limits the use of these drugs. A variety of markers are being explored to prolong the renal graft life. One of these molecules, monocide chemoattractant protein (MCP-1) is a marker involved in renal inflammation. The production of MCP-1 was blocked in kidney diseases and the disease was improved. Along with these promising developments, we decided to investigate whether there is a significant relationship between immunosuppressive therapies used in renal transplantation therapy and serum MCP-1 levels. Our study was performed in 80 patients who underwent kidney transplantation followed in Haydarpaşa Numune Training and Research Hospital. These 80 patients were examined in 4 groups as Group 1 (cyclosporin), Group 2 (tacrolimus), Group 3 (sirolimus) and Group 4 (everolimus). Serum MCP-1 levels were compared between the groups by using ELISA method. In our study, serum MCP-1 levels were significantly higher in cyclosporine and tacrolimus groups than in sirolimus (p<0.05). When calcineurin inhibitors and everolimus were compared, it was not statistically significant, although calcineurin inhibitors were higher. Understanding the role of MCP-1 in monocyte homeostasis and the effects of MCP-1 inhibition in kidney disease will help to design better diagnostic and treatment strategies in patients with inflammatory kidney disease (Tab. 2, Fig. 7, Ref. 45).

A comparative study of efficacy, tolerability and safety of 0.03% tacrolimus eye ointment and 0.05% cyclosporin eye drops in the treatment of vernal keratoconjunctivitis

Background: Vernal keratoconjunctivitis (VKC) is a common, chronic, bilateral, recurrent, allergic, inflammatory disease of the ocular surface primarily affecting young males in dry, hot climates such as India.Objectives: To compare the efficacy, tolerability and safety of 0.03% tacrolimus eye ointment and 0.05% cyclosporin eye drops in the treatment of vernal keratoconjunctivitis. Methods: A prospective study of 72 patients conducted from December 2017 to February 2021. After having established a diagnosis of VKC and fulfilling inclusion and exclusion criteria, participants were divided into two groups. Group 1 was put on cyclosporin eye drops and group 2 was put on tacrolimus eye ointment. Detailed history and evaluation for symptoms, signs, visual acuity and IOP was done on first visit and subsequently after 6 weeks, 12 weeks and 24 weeks. Results: 72 patients were diagnosed to have VKC, of whom males were 86% and females 13.9%, all belonging to the age group 5 to 14 years and were divided into two groups. Both the groups showed significant reduction in the symptoms and signs with no significant difference in efficacy between the groups and they maintained normal IOP and visual acuity at 6 weeks, 12 weeks and 24 weeks.Conclusion: Both the immunomodulators were equally successful in resolving the signs and symptoms of VKC, tolerable with no significant adverse effects and proved to be a safer alternative to steroids as they caused no elevation of intraocular pressure or any complications associated with the use of steroids.