A Real-World Claims Database Study Assessing Long-Term Persistence with Golimumab Treatment in Patients with Rheumatoid Arthritis in Japan

Patient Characteristics

A total of 384,983 records of patients with RA were identified from the MDV database, of which 7524 were prescribed GLM. A total of 39,545 patients were prescribed JAK inhibitors or any other bDMARDs but not GLM and 11,995 of them who met the inclusion/exclusion criteria were considered as the reference cohort for analysis (Fig. 2). Of the 7524 GLM-treated patients, 2283 were never prescribed bDMARDs or JAK inhibitors prior to GLM (naïve), 942 were prescribed one bDMARD or JAK inhibitor prior to GLM [switch (1)], and 322 were prescribed at least two other bDMARDs or JAK inhibitors prior to GLM [switch (≥ 2)]. Figure 2 depicts an overview of the stratified patient demographics of naïve, switch (1), and switch (≥ 2) patients.

Fig. 2figure 2

Flow diagram of patient disposition demonstrating the number of patients included in each population of the GLM cohort study or all bDMARDs and JAK inhibitor cohort study. bDMARDs biologic disease-modifying anti-rheumatic drugs, GLM golimumab, JAK Janus kinase, RA rheumatoid arthritis

The mean age of the patients in the naïve group (67.3 years) was slightly but significantly higher than the mean age of the patients in the switch (overall) group (66.5 years), p = 0.047. There was no significant difference in the mean age of patients in the switch (1) group (p = 0.106) versus the switch (≥ 2) group (p = 0.717). The majority of patients were women (naïve group, 78.84%; switch group, 81.41%) and switched patients had slightly higher CCI scores (CCI score of 3–5, naïve group [23.04%] vs switch group [30.30%]) and had higher morbidity than naïve patients at baseline (Table 1). Patients in the switch (1) group had a significantly higher rate of congestive heart failure (p = 0.010), peripheral vascular diseases (p = 0.009), chronic lung diseases (p < 0.001), ulcers (p = 0.003), diabetes without chronic complications (p = 0.005), renal disease (p = 0.030), and acquired immune deficiency syndrome/human immunodeficiency virus (AIDS/HIV) (p = 0.028) than the naïve group. However, none of the differences were significant when compared to patients in the switch (≥ 2) group (p > 0.05). The prevalence of hemiplegia or paraplegia (0.57%) was found only in naïve patients. A higher percentage of naïve patients (naïve group 37.14% vs overall switch group 22.47%) were receiving concomitant high dose MTX (> 8 mg/week), while more switched patients received no MTX (MTX free, 41.46%) or low dose (≤ 8 mg/week) of concomitant MTX (36.08%). A high proportion of naïve patients (80.29% vs overall switch group 70.02%) used 50 mg of GLM as their first dose, while a high proportion of switched patients (overall switch group 29.35% vs naïve group 19.23%) used 100 mg of GLM as their first dose.

Table 1 Demographics and clinical baseline characteristicsGLM Persistence in Naïve vs Switch Groups

As per the Kaplan–Meier analyses, the persistence rate of GLM naïve patients was 58.78% (95% CI 56.73–60.77) at 1 year, 32.08% (95% CI 29.93–34.25) at 3 years, 21.42% (95% CI 18.96–23.99) at 5 years, and 11.36% (95% CI 7.54–16.02) at 7 years (Fig. 3). The persistence rate of GLM decreased with the number of drug switches compared to naïve patients. The persistence rate for switch (1) patients was 49.04% (95% CI 45.81–52.19) at 1 year, 30.29% (95% CI 27.17–33.45) at 3 years, 18.76% (95% CI 15.49–22.27) at 5 years, and 11.62% (95% CI 7.70–16.41) at 7 years. In switch (≥ 2) patients, the rates were 45.34% (95% CI 39.83–50.68%) at 1 year, 19.12% (95% CI 14.56–24.15) at 3 years, 13.98% (95% CI 9.49–19.31) at 5 years, and 5.24% (95% CI 1.40–13.05%) at 7 years (Fig. 3). The Kaplan–Meier analysis showed longer persistence in the GLM naïve group compared with the switch (1) group (p < 0.001). Similar significant difference was also observed when the switch (1) group was compared with the switch (≥ 2) group (p < 0.001). The median time to discontinuation of GLM was shorter in the switch groups compared to the naïve group [naïve, 529 days; switch (1), 358 days; switch (≥ 2), 319 days]. The time to discontinuation of GLM, especially in the naïve group (529 days), was comparable or longer than the reference cohort that includes other bDMARDs and JAK inhibitors (329 days) (Fig. 3).

Fig. 3figure 3

Persistence of GLM treatments stratified by the number of prior bDMARDs. A Kaplan–Meier analysis was conducted to assess persistence with GLM treatment during the MDV cohort surveillance period in relation to the number of previous bDMARDs (0, 1, or ≥ 2). Kaplan–Meier curves were compared with the log-rank test, using the subgroup who had previously received one bDMARD as a reference. The log-rank p values were adjusted for multiplicity by using Bonferroni correction. Descriptive statistics are presented in the table. Reference cohort: all bDMARDs and JAK inhibitors without GLM cohort. bDMARDs biologic disease-modifying anti-rheumatic drugs, GLM golimumab, JAK Janus kinase, RA rheumatoid arthritis

Effect of Baseline Factors on GLM Persistence

The Cox HR analysis was used to examine baseline demographic and clinical factors affecting GLM persistence at each GLM administration timing (Table 2). The GLM persistence rate was significantly increased by age. In the GLM-naïve group patients aged between 61 and 75 years had an increased GLM persistence rate (HR 0.84, p = 0.008). However, age had no significant effect on persistence rate in patients aged > 75 years or in the switch groups. Gender was associated with an increase in the GLM persistence rate in the naïve group (HR 0.86, p = 0.019), but there was no significant difference in switch groups. Both high-dose (> 8 mg/week) and low-dose (≤ 8 mg/week) concomitant use of MTX were significant factors in increasing the GLM persistence rate in the naïve and switch (1) groups. The HR for concomitant MTX high dose was 0.71 (p < 0.001) for the naïve group and 0.78 (p < 0.01) for switch (1) group. The HR for concomitant MTX low dose was 0.66 (p < 0.001) for the naïve group and 0.74 (p < 0.001) for the switch (1) group. CCI scores of 3–5 had higher hazards of medication discontinuation and thus were less persistent compared to the reference group in the naïve group (HR 1.19, p = 0.005) and switch group (1) (HR 1.18, p = 0.0048). Regarding the initial dose of GLM, a dose of 100 mg significantly reduced the GLM persistence rate in the switch (1) group compared to patients receiving a dose of 50 mg (HR 1.23, p = 0.022). There was no significant difference in the naïve group amongst the patients taking a dose of 100 mg or 50 mg. Overall, in the switch (≥ 2) group, there was no statistically significant influence of age, gender, CCI score (Supplementary Table S4), concomitant MTX, or initial dose of GLM on persistence rate.

Table 2 Factors affecting persistence in the naïve, switch (1), or switch (≥ 2) groups and regression resultsBaseline Factors Predictive of > 5-Year Persistence with GLM

Logistic regression analysis was used to identify baseline factors associated with achieving GLM treatment persistence for more than 5 years (Table 3). Age (61–75 years), gender (HR 0.86, p = 0.002), concomitant MTX high dose (HR 0.73, p < 0.001), concomitant MTX low dose (HR 0.70, p < 0.001) were positively associated with GLM persistence for over 5 years. Conversely, CCI score of 3–5 (HR 1.17, p < 0.001) and score > 5 (HR 1.29, p = 0.010), an initial GLM dose of 100 mg (HR 1.14, p = 0.009), one prior biologic use (HR 1.14, p = 0.006) or two or more prior biologics use (HR 1.31, p < 0.001) were identified as factors negatively associated with GLM persistence for over 5 years.

Table 3 Univariate and multivariate Cox regression analysis to identify patient characteristic variables associated with the likelihood of long-term persistence (> 5 years) with GLM treatmentEffect of Prior Biologics on GLM Persistence

To analyze whether the persistence of GLM was altered by the use of bDMARDs or JAK inhibitors prior to GLM, Kaplan–Meier analysis of each bDMARD or JAK inhibitor subgroup was performed for up to 7 years (Fig. 4). Although there were no significant differences in patient background between the subgroups (Table 4), the duration of GLM for each subgroup was as follows in descending order (Fig. 4): infliximab (IFX), 602 days (95% CI 398–882); adalimumab (ADA), 427 days (95% CI 259–693); abatacept (ABT), 355 days (95% CI 280–469); tofacitinib (TOF), 341 days (95% CI 28–not reached); etanercept (ETN), 266 days (95% CI 176–410); certolizumab pegol (CEL), 258 days (95% CI 154–772); tocilizumab (TCZ), 214 days (95% CI 154–302); and sarilumab (SAR), 196 days (95% CI 86–225).

Fig. 4figure 4

Persistence of GLM treatments stratified by first-line bDMARD therapy. The Kaplan–Meier analysis was employed to assess persistence with GLM treatment during the MDV cohort surveillance period stratified by the first-line bDMARD (IFX, ETN, ADA, CPZ, TCZ, SAR, ABT, TOF, BAR). Each subgroup curve was compared with the IFX curve by log-rank test and p values were adjusted for multiplicity using Bonferroni correction. Descriptive statistics are presented in the table. GLM golimumab, IFX infliximab ADA adalimumab, ETN etanercept, CPZ certolizumab, TCZ tocilizumab, SAR sarilumab, ABT abatacept, TOF tofacitinib, BAR baricitinib, bDMARDs biologic disease-modifying anti-rheumatic drugs, JAK Janus kinase, MDV Medical Data Vision

Table 4 Characteristics of patient demographics and clinical baseline characteristics of the switch (1) group

GLM persistence rates by subgroup over time at 1, 3, 5, and 7 years were IFX (59%, 38%, 16%, 11%), ETN (45%, 28%, 20, 13%), ADA (54%, 54%, 24%, 13%), CEL (49%, 49%. 29%, 29%), TCZ (38%, 38%, 14%, 11%), SAR (0%, 0%, 0%, 0%), ABT (48%, 48%, 18%, 9%), TOF (47%, 47%, 31%, 31%), and BAR (80%, 80%, 53%, 53%), respectively.

Furthermore, using the IFX subgroup with the longest persistence rate as a reference, the log-rank test with Bonferroni correction was used to analyze the persistence rate of each subgroup up to 7 years. The results showed significant differences in TCZ (p = 0.001), SAR (p = 0.025), and TOF (p = 0.041), indicating that switching from these drugs to GLM significantly reduced the persistence rate compared to switching from IFX to GLM (Fig. 4). After switching from other drugs to GLM, the persistence rate was lower in groups with high MTX-free rates (Table 4). In particular, in the naïve and switch (1) groups, the persistence of the GLM with MTX was improved (Fig. 5). Amongst the GLM naïve population, the persistence rate in the MTX high group was 63.92%, 34.85%, 21.58%, and 10.66%; in the MTX low group, it was 63.89%, 38.41%, 29.22%, and 21.65% when compared to MTX-free group (47.3%, 21.89%, 12.47%, and 3.57%) at 1, 3, 5, and 7 years, respectively. Similarly, in the switch (1) population, the persistence rate in the MTX high group was 54.02%, 37.01%, 21.8%, and 9.91%; in the MTX low group, it was 53.52%, 35.36%, 27.13%, and 18.41% when compared to the MTX-free group (41.6%, 21.07%, 9.21%, and 9.21%) at 1, 3, 5, and 7 years, respectively (Supplementary Table S4).

Fig. 5figure 5

Persistence by each factor with GLM treatment stratified by the number of prior bDMARDs. A Kaplan–Meier analysis was conducted to assess persistence with GLM treatment during the MDV cohort surveillance period in relation to the number of previous bDMARDs [naïve, switch (1), or switch (≥ 2)]. Kaplan–Meier curves were compared with the log-rank test, using the subgroup who had previously received one bDMARD as a reference. The log-rank p values were adjusted for multiplicity by using Bonferroni correction. GLM golimumab, MTX methotrexate

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