Methotrexate therapy of oral corticosteroid-dependent asthmatics reduces serum immunoglobulins: correlation with clinical response to therapy
Article first published online: 17 MAY 2005
Clinical & Experimental Allergy
Volume 35, Issue 5, pages 579–584, May 2005
How to Cite
Corrigan, C. J., Shiner, R. J., Shakur, B. H. and Ind, P. W. (2005), Methotrexate therapy of oral corticosteroid-dependent asthmatics reduces serum immunoglobulins: correlation with clinical response to therapy. Clinical & Experimental Allergy, 35: 579–584. doi: 10.1111/j.1365-2222.2005.02253.x
- Issue published online: 17 MAY 2005
- Article first published online: 17 MAY 2005
- Submitted 13 September 2004; revised 24 January 2005; accepted 25 February 2005
Background Concomitant methotrexate (MTX) therapy of oral corticosteroid (CS)–dependent asthmatics has been shown to spare CS therapy, but the mechanism is unknown. In a previous report, we showed that MTX increases T cell inhibition by CS. In this report we focus on effects of MTX on immunoglobulin concentrations and their possible clinical relevance.
Objective To monitor changes in circulating leucocytes and Ig in a group of these patients during MTX therapy, and to relate these changes to clinical ‘response’ as defined by oral CS reduction.
Methods Sixteen severe asthmatics dependent on oral prednisolone 15 (7.5–25) mg/day in addition to high dose inhaled CS were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. Prednisolone dosages were maintained constant for 12 weeks then reduced systematically over the next 16 weeks provided that asthma control did not deteriorate. Patients were classified a priori as ‘responders’ or ‘non-responders’ to MTX (reduction of initial oral prednisolone requirement by 50% or <50%, respectively). Patients were followed-up for a further 12 weeks after MTX withdrawal. Serum Ig and differential blood leucocyte counts were measured at baseline, 12, 28 and 40 weeks.
Results MTX therapy allowed significant, but individually variable, reductions in oral prednisolone dosages (P<0.00001) without alteration of lung function or symptoms. This was associated with significant reductions in mean serum concentrations of Ig of all classes, which reversed following MTX withdrawal. Reductions in IgE and IgG were significantly greater in the MTX ‘responders’ as compared with ‘non-responders’, and changes in IgE, IgG and IgM correlated with changes in prednisolone requirements. Differential blood leucocyte counts showed no significant variation.
Conclusion MTX therapy reduced oral CS requirements in these severe asthmatics to a degree which correlated with reduced circulating Ig but not lymphopaenia, suggesting a possible cause and effect relationship. These reductions might also contribute to the documented incidence of opportunistic infection in these circumstances.