Sulphasalazine In The Treatment Of Ankylosing Spondylitis And Rheumatoid Arthritis: Relationship Of Dose And Plasm Levels To Efficacy

[Background and objective]Sulfasalazine(SASP) is a well established disease-modifying anti-rheumatic drug(DMARD) used in the treatment of patients with ankylosing spondylitis(AS) and rheumatoid arthritis(RA). However, the response in any individual is unpredictable. Although some studies showed that dose of SASP and plasma levels of its metabolites were associated with efficacy and toxicity of SASP in rheumatic disease, the results were inconsistent. The aim of this study is to investigate the relationship of plasma levels of SASP and SP with efficacy and toxicity.[Subjects and Methods]Eighty-eight patients with AS and thirty-one patients with RA were treated with 1.5~3.0g/d of SASP. Plasma samples were taken until one month after administration, respectively. Plasma concentrations of SASP and SP were determined by the HPLC method. Patients followed up at least 3 months were involved in efficacy assessment. Therapeutic efficacy were evaluated according to ASAS 20 for AS and ACR 20 for RA patients. The adverse reaction (ADR) of SASP was evaluated according to the associate evaluation of ADR recommended by National ADR Center. 1.50g/d SASP was defined low-dose and 2.25~3.00g/d was defined high-dose.[Results]Ninety patients including 24 RA and 66 AS followed up at least 3 months were involved in efficacy assessment. 14 patients with RA achieved ACR 20 and 45 patients with AS achieved ASAS 20. The plasma levels of SASP and SP are higher in the effective group than the not(SASP: 9.3±10.9μg/ml vs. 6.8±7.1μg/ml, P=0.265; SP: 6.8±6.4μg/ml vs. 5.4±5.1μg/ml, P=0.302), and also the frequencies of high dose(45.8% vs. 22.6%,P=0.025), only the difference of dose achieved significance at the 5% level using chi squared analysis.Adverse reactions of gastrointestinal tract and central nervous system were found in 30(25.2%) out of 119 patients. The plasma levels of SASP and SP are lower in the patients with ADR than without(SASP: 8.6±8.1μg/ml vs. 10.4±13.2μg/ml,P=0.499; SP: 6.1±5.3μg/ml vs. 7.3±7.1μg/ml, P=0.304), but the difference did not achieve statistic significance.[Conclusions]The efficacy of SASP in RA and AS is dose dependent in the range of 1.5g/d to 3.0g/d of SASP, and the plasm levels of SASP and SP are higher in effective group than the not. The adverse reaction to SASP is not related to the dose of SASP and plasma levels of SASP and SP. These data suggest that it may be effective and safe to increase the dose mildly for patients with poor response and no adverse reaction in low dose.