Statistical Methods
Change from baseline analyses for the continuous variables SF-36 MCS, SF-36 PCS, PSAB, WPAI, and MCID were conducted using a modified baseline observation carried forward (mBOCF) method. Change from baseline analyses for the categorical variables itch NRS, skin pain VAS, and DLQI were conducted using a modified non-responder imputation (mNRI) method. Missing data were imputed using a mBOCF method for continuous variables and a mNRI method for categorical measures.
Change from baseline analyses for the continuous variables SF-36 MCS, SF-36 PCS, PSAB, WPAI, and MCID were conducted using a modified baseline observation carried forward (mBOCF) method. Change from baseline analyses for the categorical variables itch NRS, skin pain VAS, and DLQI were conducted using a modified non-responder imputation (mNRI) method. Missing data were imputed using a mBOCF method for continuous variables and a mNRI method for categorical measures.
RESULTS
Patients
An overview of patient demographics and baseline disease characteristics for the long-term extension populations in UNCOVER-1 and UNCOVER-2 are presented in Table 1. The mean age of patients was 44.9 years and 41.9 years in UNCOVER-1 and UNCOVER-2, respectively. In both studies, approximately two thirds of the patients were male. The mean itch scores were 6.7 and 6.6, the mean skin pain VAS scores were 42.1 and 45.9, and the mean DLQI total scores were 12.2 and 12.1 in UNCOVER-1 and UNCOVER-2, respectively.
The proportion of patients that discontinued treatment over the long-term extension portion of the studies (weeks 60–264) was 20% in UNCOVER-1 and 13% in UNCOVER-2. The proportion who discontinued due to a lack of efficacy was 3% and 0% in UNCOVER-1 and UNCOVER-2, respectively. The proportion who discontinued due to an adverse event (AE) was 4% and 3% in UNCOVER-1 and UNCOVER-2, respectively. No discontinuations due to adverse events were related to study drug in either UNCOVER-1 or UNCOVER-2. There were no deaths during the long term extension portion of either study.
Patient-Reported Outcomes at 264 Weeks of Treatment
In patients with baseline itch NRS ≥4 in UNCOVER-1 and -2, the proportion with observed itch NRS ≥4 responses at 60 weeks (87.4% and 91.4%, respectively) was sustained through 264 weeks (82.4% and 93.1%, respectively) (Figure 1A and 1B). In patients with baseline itch NRS >0 in UNCOVER-1 and -2, the proportion with observed itch NRS=0 responses at 60 weeks (56.0% and 55.9%, respectively) was sustained through 264 weeks (51.7% and 58.5%, respectively) (Figure 1C and 1D). In patients with baseline skin pain VAS >0 in UNCOVER-1 and -2, the proportion with observed skin pain VAS=0 responses at 60 weeks (64.2% and 53.7%, respectively) were sustained through 264 weeks (59.3% and 63.1%, respectively) (Figure 2A and 1B). The proportion of patients in UNCOVER-1 and -2 with DLQI (0,1) responses at 60 weeks (80.0% and 83.3%, respectively) was sustained through 264 weeks (75.0% and 88.1%, respectively) (Figure 3A and 3B). For itch, skin pain and DLQI, the observed responses were similar to those determined by mNRI analyses (Figures 1, 2, and 3).
In UNCOVER-1 and -2, the observed mean changes from baseline in SF-36 MCS at 60 weeks (4.4 and 6.5, respectively) were sustained through 264 weeks (3.4 and 6.5, respectively) (Figure 4A and 4B). Likewise, the observed mean changes in SF-36 PCS in UNCOVER-1 and -2 at 60 weeks (4.5 and 4.0, respectively) were sustained through 264 weeks (4.4 and 4.8, respectively) (Figures 4C and 4D). The observed mean changes in PSAB in UNCOVER-1 and -2 at 60 weeks (-21.5 and -22.1, respectively) were also sustained through 264 weeks (-21.3 and -22.0, respectively) (Figure 5A and 5B). The observed changes from baseline in SF-36, SF-PCS, and PSAB were consistent with those determined by mBOCF analyses (Figures 4 and 5).
The baseline and mean changes from baseline in WPAI questionnaire psoriasis item scores at week 264 in UNCOVER-1 and UNCOVER-2 are presented in Table 2. The changes from baseline in scores for work absenteeism, presenteeism, productivity loss, and activity impairment were similar for UNCOVER-1 and UNCOVER-2 based on mBOCF analyses (Table 2). The proportion of patients who achieved MCID of 20% for work productivity loss and work activity impairment at week 264 were also similar in UNCOVER-1 and UNCOVER-2 (Table 2).
An overview of patient demographics and baseline disease characteristics for the long-term extension populations in UNCOVER-1 and UNCOVER-2 are presented in Table 1. The mean age of patients was 44.9 years and 41.9 years in UNCOVER-1 and UNCOVER-2, respectively. In both studies, approximately two thirds of the patients were male. The mean itch scores were 6.7 and 6.6, the mean skin pain VAS scores were 42.1 and 45.9, and the mean DLQI total scores were 12.2 and 12.1 in UNCOVER-1 and UNCOVER-2, respectively.
The proportion of patients that discontinued treatment over the long-term extension portion of the studies (weeks 60–264) was 20% in UNCOVER-1 and 13% in UNCOVER-2. The proportion who discontinued due to a lack of efficacy was 3% and 0% in UNCOVER-1 and UNCOVER-2, respectively. The proportion who discontinued due to an adverse event (AE) was 4% and 3% in UNCOVER-1 and UNCOVER-2, respectively. No discontinuations due to adverse events were related to study drug in either UNCOVER-1 or UNCOVER-2. There were no deaths during the long term extension portion of either study.
Patient-Reported Outcomes at 264 Weeks of Treatment
In patients with baseline itch NRS ≥4 in UNCOVER-1 and -2, the proportion with observed itch NRS ≥4 responses at 60 weeks (87.4% and 91.4%, respectively) was sustained through 264 weeks (82.4% and 93.1%, respectively) (Figure 1A and 1B). In patients with baseline itch NRS >0 in UNCOVER-1 and -2, the proportion with observed itch NRS=0 responses at 60 weeks (56.0% and 55.9%, respectively) was sustained through 264 weeks (51.7% and 58.5%, respectively) (Figure 1C and 1D). In patients with baseline skin pain VAS >0 in UNCOVER-1 and -2, the proportion with observed skin pain VAS=0 responses at 60 weeks (64.2% and 53.7%, respectively) were sustained through 264 weeks (59.3% and 63.1%, respectively) (Figure 2A and 1B). The proportion of patients in UNCOVER-1 and -2 with DLQI (0,1) responses at 60 weeks (80.0% and 83.3%, respectively) was sustained through 264 weeks (75.0% and 88.1%, respectively) (Figure 3A and 3B). For itch, skin pain and DLQI, the observed responses were similar to those determined by mNRI analyses (Figures 1, 2, and 3).
In UNCOVER-1 and -2, the observed mean changes from baseline in SF-36 MCS at 60 weeks (4.4 and 6.5, respectively) were sustained through 264 weeks (3.4 and 6.5, respectively) (Figure 4A and 4B). Likewise, the observed mean changes in SF-36 PCS in UNCOVER-1 and -2 at 60 weeks (4.5 and 4.0, respectively) were sustained through 264 weeks (4.4 and 4.8, respectively) (Figures 4C and 4D). The observed mean changes in PSAB in UNCOVER-1 and -2 at 60 weeks (-21.5 and -22.1, respectively) were also sustained through 264 weeks (-21.3 and -22.0, respectively) (Figure 5A and 5B). The observed changes from baseline in SF-36, SF-PCS, and PSAB were consistent with those determined by mBOCF analyses (Figures 4 and 5).
The baseline and mean changes from baseline in WPAI questionnaire psoriasis item scores at week 264 in UNCOVER-1 and UNCOVER-2 are presented in Table 2. The changes from baseline in scores for work absenteeism, presenteeism, productivity loss, and activity impairment were similar for UNCOVER-1 and UNCOVER-2 based on mBOCF analyses (Table 2). The proportion of patients who achieved MCID of 20% for work productivity loss and work activity impairment at week 264 were also similar in UNCOVER-1 and UNCOVER-2 (Table 2).
