Comment on: Sustained glucocorticoids tapering into phase 3 trials of anifrolumab: a post hoc analysis of the tulip one and tulip two trials. Bruce IN, et al. Rheumatology (Oxford). 2023;62(4):1526–1534.
Commented by: Professor Edward Vital, Associate Professor in Systemic Lupus Erythematosus at University of Leeds. Chair of BILAG and the Lupus Forum.
A number of different analyses have been published in the last year on a population of patients pooled from the TULIP 1 and 2 trials of anifrolumab. The present analysis is about the benefits of tapering glucocorticoids in all patients (regardless of treatment group) rather than the benefits of anifrolumab specifically. From the two tulip studies together, 375 patients had 10mg or greater per day of prednisone equivalent at baseline. Of these 375 patients, 155 achived sustained glucocorticoid taper, which was defined as reducing it to less than or equal to 7.5 mg at week 40 maintained to week 52. The other 220 of these patients did not achieve sustained glucocorticoid taper. These two groups of patients were compared for patient reported outcome measures await 52. These two groups of patients were then compared for patient reported outcome measures await 52. As expected, GC taper was more common in patients receiving anifrolumab and the patients classified as having sustained GC taper received a lower cumulative dose as well. When the two groups of patients were compared for patient reported outcome, measures a significant improvement in fatigue and quality of life was observed in association with GC taper. In patients with GC taper, 54% had a meaningful improvement in FACIT-F at 52 weeks compared with on 17% in patients without GC taper. Similar results were seen for the SF36-physical component summary, which was significantly improved in 52% versus 18%. The SF 36 mental component summary score was improved in 43% versus 8%.
There is more than one potential exclamation for these results. Obviously, the patients who reduced GC doses likely had a greater improvement in disease activity, and improved fatigue and quality of life could be due to reduced disease activity. However, glucocorticoids may themselves have contributed to worse reported outcomes. GCs may interfere with mood, quality of sleep, and cause weight gain and raised blood pressure. It is therefore worth considering in patients who are receiving long-term GCs with poor quality of life or fatigue that tapering GCs may in some cases improve those symptoms, and it may be worth adding other immunosuppressants or biologics in order to achieve the GC taper if necessary. This result is important because we are usually concerned about GCs due to concerns about long-term toxicity such as osteoporosis or cardiovascular risk. However these results suggest GC tapering is important to make people to feel better in the more immediate term as well.