The article contains results concerning combination frequency analysis for a wide number of three- to six-locus constellations of cytokine gene alleles, i.e., IL-1B T-31C, IL-6 G-174C, TNFA G-238A, TNFA G-308A, TNFA C-863A, IL-4 C-590T, IL-10 C-592A. The study was performed in a group of 104 patients with rheumatoid arthritis (RA) who were subject to basic therapy with methotrexate. An association was found between certain individual multi-locus allele combinations, and efficiency of the therapy, as defined by decrease in DAS28 index following 24 week of methotrexate treatment. An association was demonstrated between adverse effects of drugs used, and a "cytokine genotype" of the patients. Analysis of the results was carried out with respect to correlations between the levels of pro- and anti-inflammatory cytokine production and promoter polymorphisms of respective genes. We assume that further clinical research will allow to use our results as pharmacogenetic criteria in order to choose more effective personalized therapies, taking into account the genotypes of RA patients.