During the first six months of the study in which patients were treated with glucocorticoids, the addition of upadacitinib did not increase the rate of serious infections (difference -0.3 events/100 person-years; 95% confidence interval [CI] -5.4, 4.8). During the second phase of the study in which patients treated with upadacitinib had already completed their glucocorticoid taper, the rate of infections was higher for patients who were still being treated with glucocorticoids. However, the difference between these two groups was not statistically significant (-4.6 events/100 person-years; 95% CI -11.1, 2.0).
Only four opportunistic infections were noted among patients treated with 15 mg of upadacitinib daily, three of which occurred while the patients were still taking glucocorticoids. The rates of herpes zoster were the same in all groups, both before and after glucocorticoid tapering.
Overall, the message of this study seems to be that the risk of serious infection among patients with GCA is linked to their use of glucocorticoids. Shortening the length of their glucocorticoid taper by using more targeted immunosuppression may reduce that risk.
Meta-analyses have demonstrated an association between upadacitinib and herpes zoster.5 The two analyses of SELECT-GCA imply that both upadacitinib and glucocorticoids increase the risk of herpes zoster infection among patients with GCA, and that increased risk persists among patients who remain on upadactinib for remission maintenance. Reassuringly, the risk of other opportunistic infections seems low.
3. Methotrexate vs. Tocilizumab
Samson et al, Abstract 08916
Randomized clinical trials have supported the use of both methotrexate and tocilizumab in patients with GCA, but the efficacy of these agents have not previously been studied against each other in a single randomized trial. METOGiA was an open-label clinical trial of 218 patients with GCA, 74% with new-onset disease and 26% with relapsing disease. Patients were randomized to receive either 162 mg of subcutaneous tocilizumab weekly or 0.3 mg/kg (but no more than 20 mg) of methotrexate weekly for 52 weeks in addition to a glucocorticoid taper of 42 weeks for patients with new-onset GCA and 36 weeks for patients with relapsing disease. The study’s primary outcome was the proportion of patients without relapse measured at week 78, which was 26 weeks after treatments were discontinued.
By week 78, more patients treated with tocilizumab remained relapse free while adhering to the prespecified prednisone taper than patients who were treated with methotrexate (46% vs. 37%). The difference between the two groups was not statistically significant (9% difference, 95% CI -4%, 22%). Five patients treated with methotrexate developed Pneumocysitis infection. Altogether, seven deaths occurred in the study, six of which were in patients treated with methotrexate.
