Ciclosporin in Autoimmune Diseases — Side Effects (with Emphasis on Renal Dysfunction) and Recommendations for Use

Graffenried, B. von; Harrison, W. B.

doi:10.1007/978-3-642-70607-3_9

Cited by 15 publications

(4 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CsA produces incomplete CN inhibition in PBL of CsA-treated patients (25,26). Its safety, as shown by the low incidence of opportunistic infections (53), is due to the fact that some CN activity and thus lymphocyte responsiveness is preserved, permitting specific immune responses against infectious agents and preventing immunodeficiency. Thus CsAtreated patients can reject allografts (54), express abundant T cell cytokines (55), and be immunized against exogenous antigens (56).…”

Section: Discussionmentioning

confidence: 99%

Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

Batiuk

Kung²,

Halloran³

1997

J. Clin. Invest.

View full text Add to dashboard Cite

Cyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-␥ and IL-2 mRNA accumulation, and IFN-␥ production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-␥ production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed. ( J. Clin. Invest. 1997.

show abstract

Section: Discussionmentioning

confidence: 99%

Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

Batiuk

Kung²,

Halloran³

1997

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…A monotherapy with ciclosporin also appears to reduce the frequency of relapses significantly. Because of the still unknown late complications, ciclosporin therapy should be restricted to medical services having experience with the drug and technical possibility of measuring the blood levels [44,45]. New, less toxic, immunosuppressive drugs may improve the benefit-risk relation for these patients in the future.…”

Section: Discussionmentioning

confidence: 99%

Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study

Kahaly¹,

Schrezenmeir²,

Krause³

et al. 1986

Eur J Clin Investigation

185

View full text Add to dashboard Cite

Forty patients with Graves' ophthalmopathy stages III-V were divided into two groups in a random manner according to their year of birth. Group I received prednisone in decreasing dosage. Group II received prednisone at a comparable dosage and ciclosporin. Steroids were discontinued after 10 weeks in the two groups. In the patients of group II, ciclosporin was continued over 12 months. The therapeutic effect was assessed by an activity score based on subjective and objective symptoms (computerized tomography and sonography of the orbit, Hertel values, clinical findings). All signs of endocrine ophthalmopathy improved significantly in both groups (P less than 0.01 in group I; P less than 0.001 in group II). The improvement was significantly greater in group II (P less than 0.05) according to the predefined score. After corticosteroids were discontinued, inflammatory signs recurred in nine patients in group I and in one of group II. During the observation period of 12 months, relapses occurred in eight out of twenty patients in group I and in only one out of twenty in group II. Muscle thickness decreased in nine patients in group II, 6 months after beginning therapy. At this time, the results were not influenced in any of the twenty patients in group I. Microsomal antibodies decreased significantly (P less than 0.001) in the ciclosporin group, whereas no change was seen in the other group. Renal values rose within the normal range in group II. In this group, an infection with Klebsiella pneumoniae occurred in one patient after 4 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…At present it is advised that blood levels higher than 600-800 ,ug/ml should be avoided for cyclosporin treated patients with an autoimmune disease. 17 Moreover, the concomitant treatment with NSAIDs might have led to gastrointestinal disturbances and nephrotoxicity. Besides nephrotoxicity due to NSAIDs, 18 the kidney in rheumatoid arthritis patients can be directly involved owing to the disease.19 An increased incidence of disturbances of the upper gastrointestinal tract in rheumatoid arthritis patients has been reported, but it is not clear whether this is related to the drug treatment or represents a systemic manifestation of the disease.2t…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

Rijthoven¹,

Dijkmans²,

Hermans³

et al. 1986

Annals of the Rheumatic Diseases

104

View full text Add to dashboard Cite

SUMMARY The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs.

show abstract

Ciclosporin in Autoimmune Diseases — Side Effects (with Emphasis on Renal Dysfunction) and Recommendations for Use

Cited by 15 publications

References 9 publications

Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

Contact Info

Product

Resources

About