From February 2018 to February 2020, 115 IBD patients (67 CD and 48 UC) initiated infliximab-dyyb treatment and were followed for 12 months (Fig. 1). Of 115 patients who completed the baseline visit (visit 1), 109 completed the 3-month visit (2), 99 completed the 6-month visit (3), and 84 completed the 12-month visit (4). Among the CD cohort, 20 (29.9%) had B1 (non-stricturing, non-penetrating disease). Among the UC cohort, 28 (58.3%) had E3 extensive disease. Overall, 24 (20.9%) patients had a history of IBD-related surgery. A total of 66 (57.3%) patients received endoscopy at baseline (Table 1), and 37 had endoscopy during the follow-up period. Of 66 patients, 60 patients (90.9%) received colonoscopy, and 6 (9.1%) received sigmoidoscopy. The most common reasons for endoscopy were routine surveillance (n = 22; 33.3%), diagnosis (n = 18; 27%), and assessment for disease activity (n = 22; 33.3%).
Infliximab-dyyb Utilization Patterns
Of 115 patients, 39 were biologic naïve, 57 were switched from RP infliximab, and 19 were switched from other biologics. Patient demographics are summarized in Table 1. There were no statistically significant demographic differences between groups except in BMI.
In patients switching from RP infliximab, the majority (80.4%) of patient reasons for infliximab-dyyb treatment initiation were related to reimbursement, insurance coverage, or out-of-pocket costs. In biologic-naïve patients, the most frequent reasons for infliximab-dyyb treatment initiation were targeted therapy (64.1%), improved efficacy (15.4%), and new drug availability (12.8%).
Thirty-three patients had dose escalation at some point during the follow-up [16 (41%) in biologic naïve, 12 (21%) in patients switching from RP infliximab, and 5 (26%) in patients switching from other biologics]. A total of 13 patients had dose reductions at any time during the follow-up period [9 (23%) in biologic naïve, 3 (5%) in patients switching from RP infliximab, and 1 (5%) in patients switching from other biologics.]
Thirty-one patients in total (27%) did not reach 12 months’ follow-up. Six patients discontinued due to an AE, 1 discontinued due to lack of efficacy, 17 were lost to follow-up, 3 patients chose to withdraw, and 4 patients discontinued for other reasons. The 6 AEs that caused study withdrawal were 1 development of antidrug antibodies, 1 case of community-acquired pneumonia, 1 hypersensitivity reaction, 1 liver abscess, 1 case of drug-induced lupus, and 1 case of psoriasiform dermatitis and joint pain.
Descriptive results for clinical outcomes are presented in Table 2. Figures depicting remission and response results over time are presented in the Supplementary Material. In CD patients during the follow-up period, HBI scores did not change significantly. Mean (SD) HBI scores were 3.45 (3.04) at baseline, 3.11 (3.27) at 3 months’ follow-up, and 2.98 (2.61) at 12 months’ follow-up (p = 0.3988).
In UC patients, the mean (SD) baseline pMAYO score was 3.85 (3.05). The pMAYO score improved significantly, to 1.44 (1.94) at 3 months’ follow-up and 0.90 (1.47) at 12 months’ follow-up (p < 0.0001). Among UC patients who were biologic-naïve, pMAYO scores improved significantly over the course of the intervention, from a mean (SD) of 5.67 (2.25) at baseline to 1.41 (1.42) at 3 months’ follow-up and 1.09 (1.22) at 12 months’ follow-up (p < 0.0001). Among the subgroup of UC patients switched from RP infliximab, the pMAYO score did not change significantly over the course of the intervention, from a mean (SD) of 1.38 (1.83) at baseline to 0.56 (1.20) at 3 months’ follow-up and to 0.29 (0.85) at 12 months’ follow-up (p = 0.0103).
At baseline, 35.4% of enrolled UC patients were classified as in remission (Table 2). At 12 months’ follow-up, 87.1% of enrolled UC patients were classified as in remission (p < 0.0001). In UC patients who were biologic naïve, 5.6% were classified as in remission at baseline. This proportion increased significantly at 12 months’ follow-up to 90.9% (p = 0.0015). UC patients switched from RP infliximab indicated an improving trend for rate of remission from 71.4% at baseline to 94.1% at 12 months’ follow-up; however, it was not statistically significant (p = 0.1007).
Of the enrolled CD patients, 72.7% were classified as in remission at baseline (Table 2). After 12 months of infliximab-dyyb treatment, 77.1% of CD patients were classified as in remission (p = 0.8011). In CD patients switched from RP infliximab, the remission rate was maintained over the duration of the study from a baseline rate of 77.8% to a 12-month remission rate of 76.7% (p = 0.1077). In CD patients, 30.8% of biologic-naïve users and 6.7% of those who switched from RP infliximab demonstrated a clinical response to treatment.
PROs improved significantly from baseline to 12 months’ follow-up in nearly all questionnaires administered to participants. Descriptive results at each visit are presented in Table 3. Results for changes from baseline from the MMRM model are depicted in Figs. 2 and 3. Higher scores reflect better quality of life in all the instruments except the WPAI, GAD-7, and PHQ-8, where lower scores reflect better quality of life. SIBDQ, EQ-VAS, all domains of WPAI, the effectiveness domain of TSQM, GAD-7, and PHQ-8 scores significantly improved from baseline to 12 months’ follow-up. Significant improvements were observed in SIBDQ scores from baseline to 12 months in each cohort (all p < 0.05). The SIBDQ score for the IBD cohort increased by 7 points at 3 months and by 9 points at the 12-month visit. Biologic-naïve users showed an improvement of 16 points, whereas patients who switched from RP infliximab showed an increase of 3 points (Fig. 2). EQ-VAS scores improved in the cohort of all enrolled patients compared to baseline (9-point improvement; p < 0.001), in biologic-naïve users (14-point improvement; p = 0.002), and in switchers from RP infliximab (5-point improvement; p = 0.010) (Fig. 2).
IBD-related impairment in daily activities, measured by the WPAI, decreased significantly in the cohort of all patients and in biologic-naïve users (all p < 0.05) (Table 3). Results from MMRM analysis indicated that the WPAI score decreased by 12 points at the 3-month visit and by 20 points at the 12-month visit for the IBD cohort. Biologic-naïve users showed a decrease of 25 points at the 3-month visit and 36 points at the 12-month visit. Switchers from RP infliximab had a decrease of 8 points by 12 months (Fig. 3). Patient-perceived treatment effectiveness, measured by the TSQM, also improved significantly in the cohort of all patients and in biologic-naïve users (both p < 0.001) (Table 3). Results from the MMRM model indicated that patient-perceived treatment effectiveness increased by 6 points at 3 months and 13 points at 12 months for the IBD cohort. Biologic-naïve users showed an increase of 17 points at 3 months and 26 points at 12 months. Switchers from RP infliximab had an increase of 2 points (Fig. 3). The PHQ-8 and GAD-7 scores decreased over time for the IBD cohort and for biologic-naïve patients, indicating improved quality of life (Table 3). Results from an MMRM analysis indicated that, for the IBD cohort, PHQ-8 and GAD-7 scores decreased by 3.15 and 2.65 at 12 months, respectively. Biologic-naïve users showed a decrease of 4.54 points and 2.65 points for the PHQ-8 and GAD-7 at 12 months, respectively. Switchers from RP infliximab had a decrease of 1.21 for the PHQ-8 and 0.39 for the GAD-7 at 12 months (Fig. 3).
Healthcare Resource Use
An IBD-related hospitalization was recorded in 9.6% of patients within the baseline period and in 1.2% of patients within the 12-month observation period (Table 4). An ED visit was recorded in 10.4% of patients within the baseline period and in 3.6% within the 12-month observation period. The mean (SD) number of non-infusion gastroenterologist visits was 0.78 (1.67) visits per patient during the baseline period and 0.69 (0.78) visits per patient at 12 months.
Fifty-nine AEs were reported in 40 (40/115; 34.8%) patients. Of these, 29 (49.2%) were mild, 23 (39.0%) were moderate, and 7 (11.9%) were severe. Twenty-two AEs occurred that were classified by the enrolling physician as related to study treatment. The most frequently reported AEs related to study treatment were: gastrointestinal disorders (n = 8; 6.95%); infusion-related reactions (n = 4; 3.5%); platelet, bleeding, and clotting disorders (n = 2; 1.72%); and hypersensitivity reactions (n = 2; 1.72%). Of severe AEs that occurred during the study period, all but one were deemed by the enrolling physician to be unrelated to the intervention. The severe AE related to infliximab-dyyb treatment was a severe hypersensitivity reaction. Overall, AEs occurred at rates consistent with the known AE profile for infliximab.