Combination Therapy Of Cyclosporine Research Articles

Combination Therapy of Cyclosporin A and Plasma Exchange for Infants with Immunoglobulin-resistant Kawasaki Disease

Combination Therapy of Cyclosporin A and Plasma Exchange for Infants with Immunoglobulin-resistant Kawasaki Disease

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.

Combination therapy of cyclosporine A and mycophenolate mofetil in rats with adriamycin-induced nephrotic syndrome

Combination therapy of cyclosporine A and mycophenolate mofetil in rats with adriamycin-induced nephrotic syndrome

Boosting effect of cyclosporine on corticosteroids in the acute management of toxic epidermal necrolysis

<p class="abstract">Toxic epidermal necrolysis (TEN) is a life-threatening dermatological emergencies. It is a rare, acute mucocutaneous disorder that usually occur secondarily as an idiosyncratic reaction to certain drugs. Prompt identification and discontinuation of the causative drug is mandatory along with adequate supportive care like proper hydration, minimize the number of skin manipulation, prevention of secondary infections. Many immunosuppressive modalities have been tried with variable results. In this manuscript, we reported 12 consecutive cases of TEN presented to our hospital over a period of 2 years from 2017 to 2019. All the cases presented with varying percentage of skin blistering and mucosal involvement secondary to an offending drug. The incriminated drug was discontinued, supportive care was initiated along with combination therapy of cyclosporine and corticosteroids as immunosuppressants. The clinical presentation, etiological drugs and treatment protocol followed and its efficacy will be described in details.</p>

Long-term efficacy and safety of infliximab and cyclosporine combination therapy for refractory uveoretinitis in Behçet's disease.

PurposeThis study aimed to evaluate the long-term efficacy and safety of infliximab (IFX) and cyclosporine (CsA) combination therapy for refractory uveoretinitis in Behçet’s disease (BD).Patients and methodsThe study involved a retrospective review of the medical records of 11 patients with Behçet’s uveoretinitis refractory to conventional treatment who had been treated with IFX+CsA combination therapy. The frequency of ocular inflammatory attacks and a Behçet’s disease ocular attack score 24 (BOS24) were used as indices for the evaluation of efficacy during each 6-month period prior to and following initiation of therapy. For the assessment of safety, adverse events (AEs) were recorded throughout the treatment period.ResultsThe patients had received IFX+CsA combination therapy for 5.6±2.3 years. The frequency of ocular attacks per 6-month period decreased markedly from 2.9±1.6 during the baseline period to 0.6±0.9 during months 1–6, 0.5±0.9 during months 7–12, 0.3±0.5 during months 13–18, 0.3±0.7 during months 19–24, and 0.0±0.0 thereafter (P=0.003). The BOS24 score per ocular attack significantly decreased from 5.2±2.4 during the baseline period to 1.5±2.1 during months 1–6, 1.7±3.1 during months 7–12, 1.6±2.9 during months 13–18, and 0.4±1.0 during months 19–24 (P=0.002). No serious AEs were observed, with the exception of urinary tract infection and cataract progression. Two patients exhibited transient elevation of the serum creatinine level, which was normalized following a reduction in the dose of CsA.ConclusionFor refractory Behçet’s uveoretinitis, IFX+CsA combination therapy offers a promising treatment option as it appears to have an acceptable safety profile and can reduce the frequency and severity of ocular inflammatory attacks over a long period of time.

330 - Combination Therapy of Cyclosporine and Vedolizumab is Effective and Safe for Severe, Steroid-Resistant Ulcerative Colitis Patients: A Prospective Study

330 - Combination Therapy of Cyclosporine and Vedolizumab is Effective and Safe for Severe, Steroid-Resistant Ulcerative Colitis Patients: A Prospective Study

DOP049 Combination therapy of cyclosporine and vedolizumab is effective and safe for severe, steroid-resistant ulcerative colitis patients: A prospective study

DOP049 Combination therapy of cyclosporine and vedolizumab is effective and safe for severe, steroid-resistant ulcerative colitis patients: A prospective study

Combination therapy of cyclosporine and prednisolone in a dog with systemic lupus erythematosus

Abstract : An 11-year-old, spayed female poodle presented with fever and shifting lameness. Physical examinationrevealed hyperthermia (40.6 o C), and proteinuria was detected upon urinalysis. Increased neutrophils (83%) and decreasedviscosity were revealed upon synovial fluid analysis. Serum antinuclear antibody was positive at 1 : 80. Based on thesefindings, the dog was diagnosed with systemic lupus erythematosus. Immunosuppressive therapy was initiated withprednisolone and cyclosporine, and the condition was markedly improved after the treatments. This case report describesthe clinical and laboratory findings, imaging characteristics and successful outcomes after prednisolone plus cyclosporinetherapy in a canine systemic lupus erythematosus case.Keywords : antinuclear antibody, cyclosporine, glomerulonephritis, polyarthritis, systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a multisystemicautoimmune disorder in which immunity is directed againstvarious tissues or tissue components [1]. The most commonclinical features include shifting lameness from polyarthritis,ulceration of extremities caused by vasculitis, icteric and palemucous membranes resulting from immune-mediated hemol-ysis, and peripheral edema or pleural effusion due to hypoal-buminemia secondary to glomerulonephritis. Additionally,dermatologic lesions may be present, including crusting, alope-cia, erythema, ulceration, and hyperkeratosis [8].Major signs of SLE are skin lesions, non-erosive polyarthri-tis, hemolytic anemia, glomerulonephritis, polymyositis, leuko-penia, and thrombocytopenia [1]. Minor signs are fever, centralnervous system symptoms, oral ulcerations, lymphadenopa-thy, pericarditis, and pleuritis [2]. The antinuclear antibody(ANA) test and lupus erythematosus (LE) cell preparations areused clinically for the diagnosis of SLE, but until recently, theANA test is considered the most sensitive [3, 14]. Immunosup-pression is vital to treating this abnormal immune response,and patients can be treated with high dose of prednisolone (1–2 mg/kg, per oral [PO], q12h) and cytotoxic drugs, such asazathioprine, cyclosporine, and cyclophosphamide [4, 5]. Thiscase report describes successful treatment using prednisoloneand cyclosporine in a dog with SLE.An 11-year-old, 6.1 kg, spayed female poodle dog pre-sented with fever, lethargy, anorexia, and shifting lameness.The dog had a history of reluctance to stand up and walk,which was intermittent and partially responsive to non-steroi-dal anti-inflammatory drugs. Physical examination was unre-markable except for hyperthermia (40.6

Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis.

We investigated the efficacy of rituximab and low-dose cyclosporine combination therapy for focal segmental glomerulosclerosis (FSGS) in children with steroid-resistant nephrotic syndrome (SRNS). Five FSGS children with SRNS were treated twice with rituximab and low-dose cyclosporine (CyA) combination therapy (RTX-CyAT). The clinical features and laboratory data were investigated before and after RTX-CyAT, and the outcomes were assessed. Prednisolone (PSL) was discontinued 3 months after RTX-CyAT in all patients. The number of CD19-positive cells decreased to <1% of all white blood cells in all patients at 1 month after RTX-CyAT, and was maintained at this level for 259.6 ± 68.2 days. All patients remained in remission for the duration of the decrease in CD19-positive cells to <1%. Two patients also remained in remission throughout the observation period, with three patients having a single relapse at 333 ± 89 days (range, 231-376 days) after RTX-CyAT. In all patients, the mean steroid and CyA doses after RTX-CyAT were lower than those before RTX-CyAT. RTX-CyAT is effective in FSGS patients with SRNS and may ameliorate the side-effects of PSL and immunosuppressive drugs.

Combination therapy of cyclosporine and anti-tumor necrosis factor α in psoriasis: a case series of 10 patients.

Combination therapy has become important in treating psoriasis, using synergism between different mechanisms to maximize efficacy and minimize toxicity. Little has been published on the combination of cyclosporine and anti-tumor necrosis factor (TNF) α agents. In this study, a retrospective chart review was made of the effects of this combination therapy in 10 patients with recalcitrant psoriasis. Treatment included a conditioning phase with cyclosporine, 3.14 ± 0.37 mg/kg for 4.6 ± 2 weeks, and a combination phase during which etanercept/adalimumab were initiated and cyclosporine was tapered over 10.2 ± 3.7 weeks. Treatment success, evaluated after each phase, was classified as complete recovery (CR, more than 75% improvement), partial response (PR, 25-75% improvement), and no response (NR, less than 25% improvement). All patients reached CR at the end of the combination therapy. Two were still on combination therapy after 12 and 20 weeks. Adverse event occurred in three cases, all in the conditioning phase. We conclude that combination therapy with cyclosporine and anti-TNF α appears to offer an effective and safe approach to treatment of psoriasis.

ステロイド依存性頻回再発型ネフローゼ症候群に対するシクロスポリンとミゾリビン併用療法の安全性・有効性についての検討

ステロイド依存性頻回再発型ネフローゼ症候群に対するシクロスポリンとミゾリビン併用療法の安全性・有効性についての検討

Efficacy of cyclosporine combination therapy for new-onset minimal change nephrotic syndrome in adults.

BackgroundCyclosporine and prednisolone combination therapy has been used in the treatment of minimal change nephrotic syndrome (MCNS). However, few studies have evaluated the efficacy of cyclosporine combined with intravenous methylprednisolone pulse therapy (MPT) as a first-line treatment for new-onset MCNS. We conducted a retrospective clinical study to evaluate the efficacy and safety of cyclosporine combined with MPT and oral prednisolone for new-onset MCNS in adults.MethodsForty-six adult patients with biopsy-proven MCNS were analyzed retrospectively. This study included three groups. Group 1 (n = 17) was treated with intravenous MPT (0.5 or 1.0 g/day for 3 days) followed by oral cyclosporine (2–3 mg/kg/day) and prednisolone (30 mg/day). Group 2 (n = 15) was treated with intravenous MPT followed by oral prednisolone (0.4–0.8 mg/kg/day). Group 3 (n = 14) was treated with oral prednisolone (0.6–1.0 mg/kg/day) alone.ResultsThe length of hospital stay was the shortest in Group 1 (P < 0.001). The mean duration to achieve <20 mg/day of prednisolone was also the shortest in Group 1 (P < 0.05). Complete remission rates were 100 % in Group 1, 85.7 % in Group 2, and 69.2 % in Group 3 during the 9-month follow-up (P = 0.073). The rate of adverse effects caused by prednisolone was less in Group 1 (P < 0.05). Multivariate analysis revealed that the independent determinants of durations of remission were the selectivity index (P = 0.004), eGFR (P = 0.001) and the use of cyclosporine (P = 0.045).ConclusionsCombination therapy with cyclosporine may be a beneficial treatment option for new-onset MCNS in adults because of its clinical efficacy and safety.

Pulmonary alveolar proteinosis due to mycophenolate and cyclosporine combination therapy in a renal transplant recipient.

Pulmonary alveolar proteinosis (PAP) is an orphan disease characterized by the accumulation of excess of surfactant within alveoli and bronchioles. The primary form of PAP (P-PAP; also referred to as idiopathic or autoimmune) is the most common form. It is mediated through a circulating neutralizing antibody against granulocyte-macrophage colony-stimulating factor. Secondary PAP (S-PAP) can be induced by a host of inciting agents and is far more liable to progress to terminal respiratory failure. We describe a rare case of S-PAP occurring in a renal transplant recipient due to mycophenolate and cyclosporine combination-therapy, which resolved spontaneously following withdrawal of these drugs.

A retrospective analysis of combination methotrexate–cyclosporine therapy in moderate–severe psoriasis

Background: Methotrexate–cyclosprine combination therapy has traditionally been discouraged in the treatment of moderate–severe psoriasis. However, recent reports indicate that the two may be used in combination in psoriasis. Aim: The retrospective study was undertaken to study the adverse effects and efficacy of the combination in Indian patients of psoriasis. Methods: The records of all patients who received combination therapy between 2005 and 2010 were extracted. Demographic details, disease profile, presence of coexistent arthropathy, prior therapy, duration of combination therapy, body surface area involvement, Psoriasis Area and Severity Index (PASI), and adverse effects were recorded. Descriptive statistics were used to analyze the data. Results: Eighteen patients received combination therapy during the study period. Fourteen patients received short-term combination therapy and four patients received long-term combination therapy. Twelve patients in the first group and all patients of the second group achieved the primary end point of PASI by 50% from baseline (PASI 50). Nine patients in the first group and all patients in the second group suffered from significant adverse effects; they were however reversible. Conclusion: Methotrexate–cyclosporine combination therapy can be used with adequate monitoring in the treatment of moderate–severe psoriasis. Adverse effects seen are usually reversible with reduction in dose and cessation of therapy. Adverse effects related to cyclosporine are a common problem.

Combination Therapy with Cyclosporine and Psoralen Plus Ultraviolet A in the Patients with Severe Alopecia Areata: A Retrospective Study with a Self-Controlled Design

BackgroundAlopecia areata (AA) is believed to be an organ-specific autoimmune disease in which a mononuclear cell infiltrate develops in and around anagen hair follicles. There is no definitive therapy for AA.ObjectiveWe sought to determine whether the combination therapy of cyclosporine and psoralen plus ultraviolet A (PUVA) could be an effective treatment for severe AA.MethodsA total of 41 patients with severe AA were treated with oral cyclosporine and topical PUVA. Cyclosporine was given at an initial daily dose of 200 mg for adult and 100 mg for children for periods of up to 16 weeks. Eight-methoxypsoralen (Methoxsalen) was applied topically 20 minutes prior to ultraviolet A (UVA) exposure, and the patients were irradiated with UVA twice a week for 16 weeks.ResultsOf the total 41 patients, 2 (7.3%) patients were lost to follow-up, and 1 (2.4%) patient discontinued the treatment due to abdominal discomfort. Six (14.6%) patients were treated for less than 12 weeks. Of remaining 32 patients, 3 (9.4%) showed excellent response, 3 (9.4%) showed good response, 12 (37.5%) showed fair response, and 14 (43.7%) showed poor response.ConclusionAlthough limited by its uncontrolled character, this study shows that the combination therapy with cyclosporine and PUVA may be an additional choice for severe and recalcitrant AA.

Plasma cell hepatitis (de-novo autoimmune hepatitis) developing post liver transplantation

Cases of de-novo autoimmune hepatitis/plasma cell hepatitis (PCH) are increasingly being diagnosed by liver transplant centers. Its pathogenesis is poorly understood but this entity appears to be a variant of rejection. Herein, we review recent clinical reports of patients developing PCH. Histologically, PCH is a challenging diagnosis, especially in the setting of recurrent hepatitis C and, in some cases, can be mistaken for acute cellular rejection. Recent case reports and case-control studies have shown that interferon appears to trigger PCH in hepatitis C posttransplant patients. Optimization of the immunosuppression regimen was found to prevent the development of PCH. In the nonhepatitis C posttransplant patient, tacrolimus-based immunosuppression appears to have some protective effect from PCH development. A combination therapy of cyclosporine and everolimus has also been shown to be effective in treating PCH. PCH is a variant of rejection and is a cause of late graft loss post liver transplantation, especially in patients with hepatitis C. It should be part of the differential diagnosis of abnormal liver enzyme tests occurring in the post-liver transplant setting.

シクロスポリン・ミゾリビン併用療法再開が奏効したリツキシマブ治療後の難治性ネフローゼ症候群2症例

シクロスポリン・ミゾリビン併用療法再開が奏効したリツキシマブ治療後の難治性ネフローゼ症候群2症例

Dyskeratosis Congenita: Evaluation of Immune Status and Hematopoietic Stem Cell Transplantation. A Literature and EBMT Data Base Survey of 75 Patients,

Abstract 4144Dyskeratosis congenita (DC) is a rare inherited disease characterized by mucocutaneous abnormalities, progressive hematopoietic bone marrow failure as well as a predisposition to pulmonary fibrosis and malignancies. Unknown is if the lymphocytic lineage is affected as well. DC is a disease of defective telomere maintenance; the known mutations are located in the telomere biology genes DKC1, TERC, TERT, TINF2, NHP2 and NOP10 with X-linked, autosomal dominant and recessive inheritance patterns. Allogeneic stem cell transplantation (SCT) is the only potential curative treatment for bone marrow failure in patients with classical DC; however available data on SCT is scarce. Our objectives in this retrospective literature and database study on classical DC were to evaluate immune status at diagnosis, transplant procedures performed, engraftment, complications and survival.Data from all accessible English, French, German and Dutch articles of PubMed, UptoDate, EMBASE and Cochrane presenting classical DC patients with SCT were collected in a DC specific database. Corresponding authors were asked for additional data and for registration at the European Blood and Marrow Transplantation group (EBMT) database to prevent double inclusion. Forty-seven patients were found this way. From the EBMT Working Parties Inborn Errors and Severe Aplastic Anemia data bases we included 28 patients. In total 75 patients with DC who underwent 83 SCTs (8 patients were grafted twice) were included.Immune status at diagnosis could be studied in 26 patients, comparing data to age-matched controls. One or more decreased lymphocyte subset counts (CD3, CD4, CD8, NK or B cells) were found in 9/13 evaluable patients (69%) while IgG, IgM and IgA values were normal in 16/22 evaluable patients (73%).For the whole group, data on gene mutations were only available for 6 patients; data on 13 cases are pending. Median age at SCT was 11.1 (1.0–28.8) years. Most donors were matched siblings, matched unrelated or mismatched unrelated (n=32, 20, and 10, resp.). Stem cell source was BM in 56, PB in 7 and CB in 9 cases (unknown, 3). Conditioning was myeloablative in 30, reduced intensity (RIC) in 32 and unknown in 13 cases without difference in engraftment and chimaerism but with a tendency towards less TRM and better survival in RIC. Acute graft-versus-host-disease (GvHD) grade II-IV was seen in 13/54 evaluable cases, chronic GvHD in 13/50 evaluable cases. Cyclosporine monotherapy was associated with an OR of 5.5 (CI 1.073–28.198) for chronic GvHD when compared to cyclosporine combination therapy. Alive at last follow-up were 34/75 patients; causes of death in 11/26 evaluable patients were transplant related in 6/11 and DC related in 5/11. Probability of survival was 66% at 5 years and 28% at 10 years post SCT. Pulmonary fibrosis was diagnosed in 6/75 cases; malignancies in 3/41 evaluable cases.This is the largest study ever conducted on immune status and SCT in DC suggesting an immune defect inherent to DC and a superiority for reduced intensity conditioning. DC related complications are the main cause of death later than 5 years after SCT, underlining the need for prolonged follow-up after SCT.At this moment we are adding data of another 8 patients from the Eastern Mediterranean Bone Marrow Transplant group. Continuing international collaboration is vital to understand the immune defect which could be primary related to the genotype or secondary to general attrition of rapidly dividing cells with inefficient telomere maintenance, and find ways to improve transplant procedures in this rare disease, classical DC. Disclosures:No relevant conflicts of interest to declare.

低用量ステロイドとシクロスポリン併用が奏効したＨｙｐｅｒｅｏｓｉｎｏｐｈｉｌｉｃ Ｓｙｎｄｒｏｍｅの１例

30歳，男性。2005年11月より四肢にそう痒を伴う丘疹，紅斑と鼠径部リンパ節腫脹が出現した。近医で治療を受けたが症状は改善せず，著明な好酸球増多を認めたため，2006年3月に当科を紹介された。当初は病理所見と合わせ好酸球性膿疱性毛包炎を疑い治療したが，次第に皮疹は悪化した。さらに下肢の腫脹や足背のしびれが出現し，好酸球増多も持続した。組織学的に，好酸球は脂肪織から筋膜，鼠径リンパ節へも浸潤しており，MRI検査では心筋の変性が疑われた。以上のことから本症例を hypereosinophilic syndrome と診断した。治療はステロイド内服を開始したところ，症状，好酸球数とも改善した。しかしステロイド減量に伴い好酸球数の増加を認めたため，シクロスポリンを併用し，症状はよくコントロールされた。その後，イマチニブ投与を試みたが効果はなく，最終的に低用量ステロイドとシクロスポリンを併用した結果，症状の再燃はない。なお FIP1-like1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA )融合遺伝子は陰性であった。

A Clinical Trial of Combination Therapy with Etanercept and Low Dose Cyclosporine for the Treatment of Refractory Psoriasis

Over the past decade, combination therapies have become a mainstay of dermatologic care in psoriasis. Combination therapies are often more effective and safer than large dose single-agent therapies. With the emergence of new biologic therapies, dermatologists now have a wider array of tools to treat psoriasis. Although much data exists regarding cyclosporine or biologic agents alone for psoriasis, little is known about the efficacy, safety and tolerability of combination regimens. We designed a study to evaluate the efficacy and safety of etanercept and cyclosporin combination therapy in patients with refractory psoriasis. We administered oral cyclosporine (200 mg daily) and subcutaneous etanercept 50 mg weekly injections until symptoms improved, then maintained treatment at a reduced dose. Seven patients with refractory psoriasis were evaluated 4 weekly. All 7 patients showed rapid responses to combination therapy. Mean Psoriasis Area and Severity Index reductions following conditioning therapy (mean: 6.85 weeks) and maintenance therapy (mean: 56.5 weeks) were 94.9% and 93.2%, respectively. Etanercept and low-dose cyclosporine combination therapy appears to be a safe and efficacious alternative treatment strategy for patients with refractory psoriasis. The combination induced rapid improvement in patients with refractory psoriasis and dramatically improved their quality of life. Clinical studies including larger patient cohort are required to validate the safety and efficacy of this combination therapy.