Characteristics of azathioprine use and cessation in a longitudinal lupus cohort

Abstract

Objective: Guidelines for azathioprine (AZA) use in systemic lupus erythematosus (SLE), including indications for initiation and cessation, are lacking. Clinical decision-making could be improved if reasons for cessation of AZA treatment were standardised. Methods: We determined the characteristics of AZA use in a cohort of patients with SLE and evaluated reasons for AZA cessation. Patients with SLE in a single centre had longitudinal recording of disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI)-2k), laboratory investigations and treatment from 2007 to 2012. Results: Of 183 patients studied, 67 used AZA on at least one occasion. There was no significant difference between AZA users and non-users in age or American College of Rheumatology criteria. Compared with those not treated with AZA, patients treated with AZA had higher disease activity (time-adjusted mean SLEDAI 5.2 ±0.3 vs 3.8±0.3, p=0.0028) and damage (Systemic Lupus International Collaborating Clinics (SLICC)-SDI 1.6±0.3 vs 1.2±0.1, p=0.0445), and were more likely to have a positive dsDNA (p=0.0130) and receive glucocorticoids (p<0.0001). AZA therapy was ceased in 30/67 (45%) patients. The predominant reasons for cessation were treatment de-escalation 14 (47%), treatment failure 12 (40%) and toxicity 3 (10%). AZA was switched to mycophenolate mofetil (MMF) in 9/12 (75%) of treatment failures, and this choice was strongly associated with active lupus nephritis. Conclusions: AZA toxicity was uncommon, and many patients ceased therapy in the context of treatment deescalation. However, the frequent development of active lupus nephritis requiring MMF suggests the need to distinguish refractoriness, under-treatment and nonadherence to AZA in patients with SLE. These findings suggest that future studies of AZA metabolite measurement could prove valuable in the management of SLE.