Post-weighting switching rates were similar between IXE users and ADA users (31.2% vs 30.0%; P=0.608). The mean number of days (SD) to first switch was similar between IXE and ADA users (355 [184] vs 326 [192]; P=0.073). There was no significant difference in the probability of switching over 24 months between IXE and ADA users (P=0.859), as estimated using Kaplan-Meier curves (Figure 3). IXE users had a significantly lower discontinuation rate compared to ADA users (59.1% vs 65.3%, P=0.007), whereas time to discontinuation was not significantly different (Table 2). The probability of discontinuation was not significant over 24 months between IXE and ADA users (P=0.054) (Figure 4). The median time to discontinuation was 370 days (95% CI: 370-493) for IXE and 362 days (95% CI: 341-378) for ADA users. The proportion of patients who reinitiated (19.7% vs. 19.0%, P=0.695) and the mean number of days from discontinuation to reinitiation were similar in both the groups (189 vs 190; P=0.903; Table 2).
Dosing
A total of 397 IXE users and 2347 ADA users were included in the dosing analysis. Based on the package insert for IXE, the average daily dosing during the induction period was 6.7 mg/ day and maintenance period was 2.9 mg/day. In the current study, the observed daily dosing for IXE was similar in both induction (6.2 mg/day) and maintenance periods (3.0 mg/ day; Figure 5). For ADA, the recommended average daily and maintenance dosings were 5.7 mg/day and 2.9 mg/day, respectively. The observed daily dosing for ADA was 5.1 mg/day and maintenance period was 3.0 mg/day (Figure 5). Based on these results, study patients utilized the index drugs as expected based on administration guidelines for psoriasis.
Multivariate Analysis
After multivariable adjustment, IXE users had over 52% higher odds of high treatment adherence measured by PDC ≥80% than ADA users (OR=1.52, 95% CI: 1.24-1.87). IXE users had 16% lower risk of non-persistence compared to ADA users (HR=0.84, 95% CI: 0.75-0.95). IXE users had a 17% lower risk of discontinuation compared to ADA users (HR=0.83, 95% CI:0.74-0.94; Figure 6). There was no significant difference in the risk of switching between both IXE and ADA users (HR=1.06, 95% CI: 0.89-1.25).
Dosing
A total of 397 IXE users and 2347 ADA users were included in the dosing analysis. Based on the package insert for IXE, the average daily dosing during the induction period was 6.7 mg/ day and maintenance period was 2.9 mg/day. In the current study, the observed daily dosing for IXE was similar in both induction (6.2 mg/day) and maintenance periods (3.0 mg/ day; Figure 5). For ADA, the recommended average daily and maintenance dosings were 5.7 mg/day and 2.9 mg/day, respectively. The observed daily dosing for ADA was 5.1 mg/day and maintenance period was 3.0 mg/day (Figure 5). Based on these results, study patients utilized the index drugs as expected based on administration guidelines for psoriasis.
Multivariate Analysis
After multivariable adjustment, IXE users had over 52% higher odds of high treatment adherence measured by PDC ≥80% than ADA users (OR=1.52, 95% CI: 1.24-1.87). IXE users had 16% lower risk of non-persistence compared to ADA users (HR=0.84, 95% CI: 0.75-0.95). IXE users had a 17% lower risk of discontinuation compared to ADA users (HR=0.83, 95% CI:0.74-0.94; Figure 6). There was no significant difference in the risk of switching between both IXE and ADA users (HR=1.06, 95% CI: 0.89-1.25).
DISCUSSION
To our knowledge, this is the first administrative claims study that provides real-world comparative data on long-term treatment patterns of patients with psoriasis receiving either IXE or ADA in a US population. Our findings demonstrate that IXE users had higher adherence (36.3% vs 28.8%) and persistence rates (35.2% vs 28.8%) and lower discontinuation rates (59.1% vs 65.3%) compared with ADA users over a 24-month period. After adjusting for covariates in the multivariate analysis, IXE users had a lower risk for non-persistence and discontinuation and higher odds of having highly adherent treatment than ADA users. Our findings were similar to our earlier study, which was based on variable length of follow-up of 14 and 16.5 months.17
Though a shorter follow-up time, results in the prior study were relatively similar to current results. Compared to ADA users, IXE users had 19% lower risk of non-persistence ([HR=0.81, 95% CI: 0.69-0.95] vs current study [HR=0.84, 95% CI: 0.75-0.95]), and 26% lower risk of discontinuation ([HR=0.74, 95% CI: 0.62-0.88] vs. current study [HR=0.83, 95% CI: 0.74-0.94]).17 Unlike the previous study, IXE users in the current study had 52% greater odds of being highly adherent (PDC ≥80%) compared to ADA users ([OR=1.52, 95% CI: 1.24-1.87] vs previous [OR=1.22, 95% CI: 0.98-1.53]).17 Also, in the current study, no significant difference was observed in the risk of switching between IXE and ADA users ([HR=1.06, 95% CI: 0.89-1.25] vs previous [HR=0.72, 95% CI: 0.57-0.91]).
Our findings regarding real-world use of ADA are consistent with the existing literature.20-23 A study by Chastek et al showed that 40-42% of biologic-naïve patients who used commercial health plans in the US were persistent on their index drug ADA for one year.20 ADA users had 45% discontinuation rate (allowing 60-day gap).20 In another real-world study conducted in the Medicare population, treatment adherence and discontinuation rates for ADA were 40.7% and 43.4%, respectively.21 In the current study, we found lower rates of adherence (28.8%) and persistence (28.8%) and higher discontinuation rates (65.3%) among ADA users. This could be attributed to the longer follow-up period. A recent real-world data study by Feldman et al that stratified ADA users with and without metabolic conditions reported discontinuation rates of 53.9% and 48.7%, respectively, for both groups.22 The discontinuation rates were slightly lower than the current study (65.3%). The plausible reason could be that Feldman et al study disqualified discontinuation if the patient restarted treatment after reaching the allowable gap.22 The combined rate of discontinuation and reinitiation was closer to the discontinuation rate in our study. The Feldman et al. study also reported rate of PDC ≥80% (27.6% vs 26.5%) for ADA users, which is similar to PDC rates reported for the ADA cohort in our current study.22
Clinicians are faced with an increasing range of biologic therapies for their patients with moderate-to-severe psoriasis. The treatment outcomes reported here serve as a proxy for real-world drug effectiveness and tolerability. In the absence of direct evidence from head-to-head trials, these realworld data (together with existing clinical trial data), help to provide clinicians with important information about long-term effectiveness, tolerability, and persistence of psoriasis drugs.23,24 The long duration of follow-up is particularly relevant given the chronicity of psoriasis. Lastly, these real-world data on treatment patterns are relevant to payers in order to make informed decisions related to effectiveness of various biologics available for the treatment of psoriasis.25,26
Though a shorter follow-up time, results in the prior study were relatively similar to current results. Compared to ADA users, IXE users had 19% lower risk of non-persistence ([HR=0.81, 95% CI: 0.69-0.95] vs current study [HR=0.84, 95% CI: 0.75-0.95]), and 26% lower risk of discontinuation ([HR=0.74, 95% CI: 0.62-0.88] vs. current study [HR=0.83, 95% CI: 0.74-0.94]).17 Unlike the previous study, IXE users in the current study had 52% greater odds of being highly adherent (PDC ≥80%) compared to ADA users ([OR=1.52, 95% CI: 1.24-1.87] vs previous [OR=1.22, 95% CI: 0.98-1.53]).17 Also, in the current study, no significant difference was observed in the risk of switching between IXE and ADA users ([HR=1.06, 95% CI: 0.89-1.25] vs previous [HR=0.72, 95% CI: 0.57-0.91]).
Our findings regarding real-world use of ADA are consistent with the existing literature.20-23 A study by Chastek et al showed that 40-42% of biologic-naïve patients who used commercial health plans in the US were persistent on their index drug ADA for one year.20 ADA users had 45% discontinuation rate (allowing 60-day gap).20 In another real-world study conducted in the Medicare population, treatment adherence and discontinuation rates for ADA were 40.7% and 43.4%, respectively.21 In the current study, we found lower rates of adherence (28.8%) and persistence (28.8%) and higher discontinuation rates (65.3%) among ADA users. This could be attributed to the longer follow-up period. A recent real-world data study by Feldman et al that stratified ADA users with and without metabolic conditions reported discontinuation rates of 53.9% and 48.7%, respectively, for both groups.22 The discontinuation rates were slightly lower than the current study (65.3%). The plausible reason could be that Feldman et al study disqualified discontinuation if the patient restarted treatment after reaching the allowable gap.22 The combined rate of discontinuation and reinitiation was closer to the discontinuation rate in our study. The Feldman et al. study also reported rate of PDC ≥80% (27.6% vs 26.5%) for ADA users, which is similar to PDC rates reported for the ADA cohort in our current study.22
Clinicians are faced with an increasing range of biologic therapies for their patients with moderate-to-severe psoriasis. The treatment outcomes reported here serve as a proxy for real-world drug effectiveness and tolerability. In the absence of direct evidence from head-to-head trials, these realworld data (together with existing clinical trial data), help to provide clinicians with important information about long-term effectiveness, tolerability, and persistence of psoriasis drugs.23,24 The long duration of follow-up is particularly relevant given the chronicity of psoriasis. Lastly, these real-world data on treatment patterns are relevant to payers in order to make informed decisions related to effectiveness of various biologics available for the treatment of psoriasis.25,26
