Information on cyclosporine as a treatment for psoriasis.

Cyclosporine is a medication administered orally and used for various types of diseases, including for the psoriasis. It has the ability to block certain cells that play a role in immune responses thus acting as an immunosuppressive drug that demonstrates an efficacy similar to that of the methotrexate.

What are the molecular mechanisms through which cyclosporine acts on psoriasis?

Cyclosporine has the ability to inhibit the activation of T lymphocytes by reducing the levels of nuclear factors in T cells, thereby decreasing the production of inflammatory cytokines. Cyclosporine also has an effect on dendritic cells and in reducing the genes of the Th17 pathway, by lowering the levels of tumor necrosis factor (TNF), inducible nitric oxide synthase, as well as IL-23p19, IL-17, and IL-22. As a reminder, the Th17 pathway plays a direct role in the onset of psoriasis.

Ciclosporin treatment is administered orally in the form of 10, 25, 50, and 100 mg capsules. The treatment should be taken twice a day, once in the morning and once in the evening. The amount of ciclosporin to be taken depends on both the weight of the individual and the nature of the disease being treated.

Generally, the treatment begins with a dosage ranging from 2 mg/kg to 5 mg/kg per day. Studies have shown that cyclosporine at doses of 2.5 to 5 mg/kg per day over a period of 12 to 16 weeks results in a rapid and significant improvement of psoriasis in 80 to 90% of patients.

For psoriasis, the duration of treatment with cyclosporine can range from a few months to several years, depending on tolerance and effectiveness. Generally, it is recommended to limit continuous treatment to a maximum of two years.

The effectiveness of the treatment varies from one patient to another. As a general rule, a significant improvement in psoriasis is observed in 60 to 80% of patients. Maximum effectiveness is typically achieved after about 3 to 4 months of treatment and is maintained during the course of treatment in most cases. Often, the first positive signs of treatment become noticeable after a month. When treatment is stopped, skin lesions reappear on average between 2 and 4 months. However, the severity of the skin condition is generally less pronounced than before the start of treatment.

Some adverse effects have been reported following treatment with cyclosporine.

• Common adverse effects.

  Common adverse effects often occur at the beginning of treatment. They may include fatigue, finger tremors, tingling sensations in the fingers or feet, headaches, and muscle pain. These effects are observed in 10 to 20% of patients. Digestive problems, such as nausea, abdominal pain, and diarrhea, may also be observed at the start of treatment.

• Impairment of kidney function.

  An impairment of kidney function can occur during prolonged treatments with cyclosporine. If this were to happen, it would be necessary to reduce the dosage or discontinue the treatment. This adverse effect is reversible upon cessation of treatment, hence the importance of close monitoring.

• Occurrence of infections.

  Furthermore, cyclosporine can reduce the body's immune defenses, thereby promoting the occurrence of infections. If you experience a fever during treatment, it is imperative to consult your doctor.

• May increase the risk of skin cancers in certain cases.

  In patients who have undergone numerous sessions of phototherapy (especially PUVA), the treatment can increase the risk of developing skin cancers. Therefore, it is essential to have regular monitoring by a dermatologist and to consult in case of the appearance of new skin lesions.

It is crucial to avoid the use of certain medications, as incompatibilities can occur between some of them and cyclosporine. Some drugs enhance the renal toxicity of cyclosporine, particularly non-steroidal anti-inflammatory drugs and aminoglycosides. It is important to inform your doctor that you are taking a cyclosporine-based treatment in order to check any new drug prescription to prevent interactions.

The treatment does not affect fertility, but breastfeeding is contraindicated. For pregnant women, cyclosporine can be used in cases of severe psoriasis that is resistant to narrow-band UVB phototherapy, as it does not cause fetal malformations. However, it can increase certain pregnancy complications, such as high blood pressure and prematurity. Therefore, the continuation or introduction of cyclosporine treatment during pregnancy requires close and specific monitoring, and the treatment should be reevaluated on a case-by-case basis.

The use of cyclosporine is not recommended for patients suffering from chronic infections, such as Hepatitis C Virus (HCV) infection. Indeed, due to the strong immunosuppressive nature of cyclosporine, it makes patients more susceptible to bacterial, viral, and fungal infections.

In general, a regular follow-up with your doctor and dermatologist is necessary during the treatment.

• GROSSMAN R. M. & al. Long-term safety of Cyclosporine in the treatment of psoriasis. Archives of Dermatology (1996).

• ROSMARIN D. M. & al. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation* Consensus Conference. The American Academy of Dermatology (2009).

• Lettre d’information pour le traitement du psoriasis par la ciclosporine orale. Groupe de recherche sur le psoriasis de la Société française de dermatologie. Annales de Dermatologie et de Vénéréologie (2011).

• Ciclosporine orale. Association France Psoriasis (2020).