Comparison of oral pulse methotrexate with placebo in the treatment of severe glucocorticosteroid-dependent asthma

Glucocorticoid-resistant asthma: more than meets the eye

“…Cyclosporine and gold showed some benefit however their usage has been limited by side effects (52). Two randomized placebo-controlled studies in steroid dependent asthmatics have shown methotrexate to have a significant steroid sparing effect with patients having fewer exacerbations and acceptable side effects (53,54). As patients vary in their response 15 to drugs, usage of methotrexate warrants close monitoring of side effects and continual evaluation of its benefit.…”

“…Cyclosporine(52) Gold(52) Methotrexate(53,54) Anti-Ig E: Omalizumab, reduces frequency of asthma exacerbations and emergency room visits(55,56) Cytokines and Cytokine inhibitors: Modulation of cytokines playing an important role in SRA and inflammation. TNF Alpha(57,58) Interferon (60) Mutated Anti-IL-4 blocking IL-4R subunit (Pitrakinra)(63) Anti-IL-5 (mepolizumab)(61,62) Anti-IL-9(57) Anti-IL-13 (lebrikizumab)(65) Intravenous immunoglobulin: Reduces steroid requirements but does not improve lung function(59) Chemokine receptor antagonists:(21,66) CXCR1/2 directed against neutrophils CCR3 directed against eosinophils CRTH2 directed against eosinophils and Th2 cells Miscellaneous:(21,67) MAPK inhibitors AP-1 inhibitors NF-κB inhibitors IL-10 secreting T regulatory cell inducers --------------------------------------------------------------------------------------------------------------------------------TNF: Tumor necrosis factor; IL: Interleukin; AP-1: Activated protein-1; NF--B: Nuclear factor-B; MAPK: Mitogen activated protein kinases Lung biopsy showing features of asthma: mucous stasis, goblet cell hyperplasia, basement membrane thickening, and smooth muscle hypertrophy with eosinophilic infiltrates and hemosiderin laden macrophages (H and E stain, 10x, 25x and 100x magnification) 28 Venn diagram showing various subsets of Asthma.…”

Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.

“…The clinical significance of this small decrease in prednisone is minimal. Another placebo-controlled crossover study in 24 corticosteroiddependent asthmatics found oral MTX (15/wk) was superior to placebo during a 12-wkstudy in reducing corticosteroid dose and improving symptoms (340). However, several studies have failed to substantiate clear benefit with MTX (44)(45)(46).…”

Asthma that is unresponsive to usual care

“…Methotrexate, gold and cyclosporin A have corticosteroid-sparing effects clinically that must be weighed against a serious adverse effect profile. [46][47][48][49][50][51][52][53][54] For example, low-dose oral methotrexate therapy, widely used in the treatment of rheumatologic diseases, has been reported to reduce the need for systemic corticosteroids in severe asthma, but study results have been inconsistent. 46−50 A few patients have been reported to benefit from oral gold therapy, 53,54 and intravenous immunoglobulin has been reported to be of benefit, but only in uncontrolled studies.…”