SELECT-PsA 2 was a 24-week study in which 642 patients with active PsA and an inadequate response to at least one biologic were randomly assigned to receive upadacitinib 15 or 30 mg/day or placebo. The findings were published in the Annals of the Rheumatic Diseases in December 2020.
Overall incidence of AEs
Rates of serious AEs and AEs leading to treatment discontinuation in SELECT-PsA 2 were higher among patients treated with either dose of upadacitinib than those given placebo (figure 3).
Figure 3. Overall rates of AEs, serious AEs, and AEs leading to treatment discontinuation in SELECT-PsA 2
Most frequent AEs
The most commonly reported treatment-emergent AEs occurring in at least 5% of patients in either upadacitinib group were:
- upper respiratory tract infection;
- nasopharyngitis;
- bronchitis;
- urinary tract infection;
- influenza;
- diarrhea;
- nausea; and
- increase in blood creatine phosphokinase levels.
Specific AEs
The SELECT-PsA 2 investigators highlight that there were higher rates of serious infections, herpes zoster, and opportunistic infections (excluding herpes zoster and tuberculosis) in the upadacitinib 30 mg group compared with the other treatment arms (figure 4). Both opportunistic infections – one case each of candidiasis of the trachea and oropharyngeal candidiasis – occurred in the upadacitinib 30 mg arm, and there were no cases of tuberculosis in the study.
The researchers say that rates of malignancy were comparable in the two upadacitinib arms, affecting three patients in each group. There were no reports of adjudicated gastrointestinal perforations, and there was one case each of MACE and VTE in the upadacitinib 15 mg group.
Figure 4. Rates of specific AEs in SELECT-PsA 2
* excluding herpes zoster and tuberculosis
Laboratory abnormalities and hepatic disorders
In general, hemoglobin, neutrophil, lymphocyte, and platelet levels “remained within normal limits” during the 24-week study period in all treatment groups, and there were “few” grade 3 or 4 laboratory abnormalities seen in upadacitinib-treated patients, report the investigators. Hepatic disorders occurred in 1.9%, 8.3%, and 1.4% of patients in the 15 mg, 30 mg, and placebo groups, respectively.
Longer-term safety observations in SELECT-PsA 2
After the 24-week double-blind period, placebo-treated patients were switched to upadacitinib 15 mg or 30 mg. The 1-year data from SELECT-PsA 2 were published in Rheumatology and Therapy in April 2021, and the researchers report “no new significant safety signals.”
They say that the risk for serious infections and herpes zoster “appeared to be dose dependent,” with exposure-adjusted event rates for serious infections of 2.6 and 6.1 per 100 person–years with the 15 mg and 30 mg dose, respectively, and a corresponding 3.8 and 8.5 per 100 person–years for herpes zoster. On the other hand, the investigators report “no dose-dependent risks” for MACE, VTE, or cancer. One patient in each upadacitinib group experienced nonfatal pulmonary embolism during the study.