The combination therapy of allopurinol and thiopurine can be safe and effective in patients with IBD who have not been responsive to prior thiopurine monotherapy, according to recent study results.
In a multicenter study, researchers administered allopurinol in combination with a low dose of thiopurine to 77 patients with IBD and skewed thiopurine metabolism. Two patients received 50 mg allopurinol; the rest of the cohort received 100 mg allopurinol. Treatment adherence and adverse events were recorded, with a mean follow-up of 19 months.
After follow-up, 61% of participants experienced steroid-free remission compared with 44% in steroid-free remission before combination therapy. Patients who received 8 or more weeks of combination therapy experienced a median 6-thioguanine nucleotide concentration increase from 145 pmol/8x108 during monotherapy to 271 pmol/8x108 red blood cells while the thiopurine dosage was reduced (P<.001). The median 6-methyl mercaptopurine concentration also decreased from 10,110 pmol/8x108 to 265 pmol/8x108 over the course of treatment (P<.001). The ratio between the two concentrations decreased in all participants from 68 (range 43-124) to 1.3 (range 0.7-3.3) (P<.001).
Sixteen participants (21%) stopped combination treatment after a median duration of 2 months (range 0.3-16 months), primarily because of adverse events and lack of efficacy (six patients each). Adverse events included leukopenia, which occurred in 12 participants (16%) and required dose modification but not cessation. Other events included nausea, fatigue and malaise (three patients each). After 6, 12, 24 and 60 months, 87%, 85%, 76% and 65% of patients, respectively, remained on combination therapy, after adjusting for loss to follow-up.
“Our study showed that thiopurine and allopurinol combination therapy maintained or induced steroid-free remission with a favorable long-term safety profile in the majority of patients with a skewed thiopurine metabolism who failed conventional thiopurine monotherapy,” the researchers wrote. “These results provide further evidence that combination therapy is effective and safe if carefully monitored and should be considered in this group of patients before escalating therapy.”