The Role of Methotrexate in the Management of Steroid-dependent Asthma – Discussion

The Role of Methotrexate in the Management of Steroid-dependent Asthma - DiscussionIn our study, low-dose methotrexate therapy did not have a significant steroid-sparing effect in severe asthma. In addition, aggressive management of asthma with close clinical follow-up improved asthma control. Furthermore, there was a small subgroup of asthmatic patients who responded to methotrexate with a significant reduction in their steroid dosage although these asthmatics had many subjective complications of their medication therapy, low-dose methotrexate does not demonstrate a significant toxicity profile.
Because the natural history of asthma is variable and compliance with medications is often poor, we designed the study so that the patient’s asthma would be optimally treated and stabilized prior to entering the study phase. This important initialization phase was not a part of many of the earlier studies. Our study extends the data of a previous study that cast doubt on the efficacy of methotrexate in asthma, utilizing a parallel study design. We chose to use a crossover study to ensure that patients were acting as their own controls. To overcome the potential cany-over of one drug effect into the following phase, we compared the parameters during the last 4 weeks of each treatment period, ensuring an effective 8-week washout period. Analysis of our results indicated that this was adequate with no carryover effect from one phase into the other. In addition, we studied patients who did not have seasonal variation in their asthma to ensure that the natural history of their asthma did not interfere with our comparison of the methotrexate with the placebo phase. buy allegra

Our study is at variance with several other studies. Inadequate stabilization of the patient’s asthma and failure to optimize their pulmonary function while receiving the minimum dose of steroids during the initial phase may be confounding variables that may lead to difficulty interpreting the results. Any improvement in the severity of asthma or reduction in the steroid dose may be attributed to the methotrexate and not to the most likely cause, which is spontaneous improvement in asthma according to the natural history of the disease. An improvement in compliance during the study period can also reduce steroid requirements. Thus, in our study, we followed up the patients for 4 to 10 weeks prior to inclusion in the protocol to ensure that their disease was stable and to optimize their pulmonary function while receiving the minimum dose of steroids.
Interestingly, despite this careful monitored initialization phase, with frequent (every 1 to 2 weeks for 4 to 10 weeks) and supportive follow-up by a physician, the steroid dose was reduced a further 20 percent during the treatment phase in patients taking the placebo. This indicates that controlled studies are essential to adequately interpret the role of medications in modifying the course of chronic disease. Enrollment in a study improves patient compliance with conventional medications, increases their awareness of their disease, and they become more confident in the benefits of therapy. The presence of a dedicated physician assessing patient progress and tapering their steroid dosage is important in the management of asthma and may have contributed to the nonsignificant difference between the reduction in steroid dosage between methotrexate and placebo groups. Clearly, a reduction in steroid therapy achieved by tighter clinical management is preferable to the addition of another potentially toxic therapy.

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