Authors’ reply

Sir,

We are thankful for the valuable comments¹ and interest shown in our article.² However, we differ regarding the idea of using methotrexate in the same dosage for both the groups. Both the drugs used in our study are known for their serious adverse effects which are related to the serum level of individual drugs. Cyclosporine is known for nephrotoxicity and methotrexate is mainly eliminated through the kidney. At the recommended doses of cyclosporine and methotrexate, there is a possibility of methotrexate toxicity. Both drugs also cause bone marrow suppression. There is also a limit to the total cumulative dose of methotrexate above which liver biopsy may be needed. Therefore, the aim was to keep cumulative methotrexate dose to the minimum while ensuring efficacy. Toxicity of cyclosporine is also dose related. Keeping all these concerns in mind, we aimed to find out whether there is a synergistic or additive effect of these two approved drugs at half of their recommended doses. Fortunately, the outcome of the study was positive and interesting. In fact, reduction of the total cumulative dose while maintaining efficacy without increasing adverse effects was our plan.

Since this is a pioneering randomised controlled trial using the combination of methotrexate and cyclosporine in the treatment of chronic plaque psoriasis, we had to ensure safety of our patients. In future, a similar study may be encouraged using a combination of the drugs at the recommended doses to remove the bias that seems to be present in using half of the recommended dose of methotrexate in one group compared to the full dose in the other group. However, whether such a dosage will be needed is questionable when using a combination of half doses is both efficacious and safe.

We are also thankful for noticing the repetition of a few adverse effects, namely nausea, vomiting, dyspepsia, anorexia, abdominal pain and fever in Table 4 as shown in our article.² It was a mistake on our part and for that we are extremely sorry. However, we would like to say that this is a technical error and since the data remain the same, we hope that it will not create a false impression about the number of adverse effects studied. We have also mentioned both in the abstract and the text that the clinical and laboratory adverse effects were comparable between the two groups.

We hope that this reply answers the queries. We agree that new combinations of therapies should be explored in dermatology to see if they are more effective without increasing adverse effects.