BackgroundIn routine care, biosimilar-to-biosimilar infliximab switching may occur to save costs (=non-medical switching). Previous studies have investigated the efficacy and safety of switches from originator infliximab to a corresponding biosimilar in patients with inflammatory rheumatic diseases (1). However, the outcomes after switching from one infliximab biosimilar to a second infliximab biosimilar remain scarcely investigated.Denmark has recently conducted a nationwide mandatory infliximab biosimilar-to-biosimilar switch.ObjectivesTo investigate the effectiveness of infliximab biosimilar-to-biosimilar switch (CTP-13 to GP1111) among patients with RA, PsA and AxSpA, including patients who had previously switched from originator (originator-experienced) to CT-P13 as well as patients who were originator-naïve.MethodsObservational cohort study based on DANBIO registry (for clinical data upon switch =baseline) linked with national patient registries (to identify prior comorbidities). Patients with RA, PsA or AxSpA who performed a biosimilar-to-biosimilar switch from CT-P13 to GP1111 between April 1st 2019 and February 1st 2020 were included. Patient were divided into two groups: originator-naïve and originator-experienced. Main outcomes in the two groups were one-year GP1111 treatment retention (Kaplan Meier “drug survival curves”) and changes in disease activity 4 months before versus 4 months after switch in individual patients. Also, factors associated with GP1111 treatment retention for both groups combined were explored with Cox proportional hazard regression analyses, stratified by diagnosis (univariate-, age-and gender adjusted and fully adjusted). Analyses were adjusted for relevant clinical factors (for details: see Table 1)Table 1.Baseline variables associated with GP1111 withdrawal (RA shown below, similar findings for PsA and AxSpA)UnivariateAge- and gender adjustedMultivariateHR (95% CI)p-valueHR (95% CI)p-valueHR (95%CI)p-valueRAFemale gender0.9 (0.6-1.3)0.4-0.7 (0.5-1.2)0.2Age, years1.0 (0.9-1.0)0.9-1.0 (0.9-1.1)0.6Originator-experienced versus originator naïve to infliximab0.5 (0.3-0.8)0.0020.5 (0.3-0.8)0.0020.4 (0.2-0.9)0.01Methotrexate use, yes0.5 (0.3-0.7)<0.0010.5 (0.3-0.7)<0.0010.6 (0.4-0.9)0.01Comorbidities ≥11.1 (0.7-1.5)0.81.1 (0.7-1.5)0.80.9 (0.6-1.4)0.7In remission (yes)0.4 (0.3-0.6)<0.0010.4 (0.2-0.6)<0.0010.5 (0.3-0.7)<0.001DAS281.7 (1.4-1.9)<0.0011.7 (1.5-1.9)<0.001--Patient global VAS, mm1.0 (1.0-1.1)<0.0011.0 (1.0-1.1)<0.001--ResultsIn total, 1,605 patients underwent an infliximab biosimilar-to-biosimilar switch and were included; 1,171 were originator-naïve and 434 were originator-experienced, 685 RA/314 PsA/606 AxSpA, median disease duration was 9 years, 42% were in DAS28/ASDAS remission at the time of switch.At one year, 83% (95% CI 81-85) of the originator-naive and 92% (95% CI 90-95) of the originator-experienced switchers maintained GP1111 treatment (Figure 1). Changes in disease activity 4 months pre- and post-switch were close to zero for all disease activity measures (e.g. DAS28, ASDAS, VAS pain, not shown).The risk of GP1111 withdrawal was lower in originator-experienced compared to originator-naïve patients in patients with RA and PsA: HR 0.4 (95% CI 0.2-0.9, p-value 0.01) and HR 0.1 (0.1-0.6, p=0.01), but not significantly for AxSpA 0.56 (0.27-1.13, p=0.1). Across all indications, lower disease activity at baseline (DAS28/ASDAS remission) was associated with higher retention (Table 1).ConclusionBiosimilar-to-biosimilar infliximab switch was effective and well-tolerated in >1,500 real-world patients. Retention was higher in originator-experienced switchers and patients, who were in remission at the time of the switch, suggesting retention to be more affected by patient-related than drug-related factors.