CT-P13 In Patients Research Articles

S1205 Fecal Calprotectin Decreases Following Transition to Subcutaneous CT-P13 in Patients With Inflammatory Bowel Diseases on Escalated Intravenous Infliximab Maintenance Therapy

S1205 Fecal Calprotectin Decreases Following Transition to Subcutaneous CT-P13 in Patients With Inflammatory Bowel Diseases on Escalated Intravenous Infliximab Maintenance Therapy

S38 Efficacy and Safety of Nonmedical Switching From Infliximab Originator to Infliximab Biosimilar CT-P13 in Patients With Inflammatory Bowel Disease, A Single-Center Prospective Study in Japan

S38 Efficacy and Safety of Nonmedical Switching From Infliximab Originator to Infliximab Biosimilar CT-P13 in Patients With Inflammatory Bowel Disease, A Single-Center Prospective Study in Japan

Real-World Safety and Efficacy of Biosimilar CT-P13 in Patients with Immune-Mediated Inflammatory Diseases: Integrated Analysis of Three Japanese Prospective Observational Studies.

Biosimilar CT-P13 was approved with limited data from clinical trials compared to the originator infliximab in biologic-naïve patients with rheumatoid arthritis. Three prospective post-marketing surveillance studies have been conducted in Japanese biologic-naïve patients and switched patients from biologics including the originator infliximab. We performed an integrated analysis of final data from three post-marketing studies to provide long-term safety and efficacy data of CT-P13 in a real-world clinical setting. A total of 1816 patients consisting of 987 patients with rheumatoid arthritis, 342 patients with Crohn's disease, 322 patients with ulcerative colitis, and 165 patients with psoriasis were evaluated for safety. Efficacy was assessed in 1150 patients whose disease parameter values were serially collected. Adverse drug reactions were reported in 24.2% of all patients. The incidence of adverse drug reactions differed by the prior treatment status with biologics: 30.5% in patients naïve to biologics, 17.0% in patients switched from the originator infliximab, and 33.5% in patients switched from other biologics. Infusion reactions were the most frequent adverse drug reactions (8.2%), and its incidence was significantly higher in patients with ulcerative colitis and an allergy history in a multivariable Cox regression analysis. Infection was the second most frequent (6.1%), but tuberculosis only occurred in four patients (0.2%). The incidence of infection was low in patients with Crohn's disease and psoriasis, and significant risk factors were an allergy history, comorbidities, and concomitant steroid use. Interstitial lung disease occurred in 16 patients (0.9%), including 11 patients with rheumatoid arthritis. With CT-P13 therapy, disease activity parameters decreased similarly in all four diseases, although long-term drug discontinuation rates because of inefficacy varied by disease. In naïve patients, the disease activity parameters decreased rapidly and the proportion of patients in remission increased. Patients switched from infliximab maintained lowered parameter levels with infliximab pretreatment. Decreases were also observed in patients switched from other biologics, but discontinuations were most often because of insufficient efficacy. The integrated analysis of a large number of patients detected no new safety signals with long-term CT-P13 treatment. Efficacy in rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis cases was confirmed in biologic-naïve patients and switched patients from the originator infliximab or other biologics.

Anti-drug antibodies and rheumatoid factor level in patients with rheumatoid arthritis using the infliximab biosimilar CT-P13

BackgroundThis study evaluated the existence of anti-drug antibodies (ADAs) before and 52 weeks after switching from intravenous infliximab (IFX) to intravenous CT-P13 in patients with rheumatoid arthritis (RA).MethodsWe performed a prospective observational study. Twenty-eight patients (7 males and 21 females) received intravenous CT-P13 after intravenous IFX, and the clinical data were collected from medical records. Rheumatoid factor (RF) and anti-CCP antibody were examined at baseline. At baseline and 52 weeks after the start of CT-P13 treatment, the Disease Activity Score based on the 28-joint count and the levels of C-reactive protein, matrix metalloproteinase-3, and ADA, as well as the erythrocyte sedimentation rate were evaluated. ADAs were measured using an enzyme-linked immunosorbent assay kit.ResultsSeven (25%) and 6 (21.4%) cases were positive for ADAs at baseline and 52 weeks after, respectively. One case became newly positive for ADAs at week 52. Two of the ADA-positive cases became ADA-negative 52 weeks after. The ADA-positive group showed significantly higher RF values at baseline than the ADA-negative group (p = 0.03). No difference was observed between the ADA-positive group and the ADA-negative group regarding other clinical parameters.ConclusionsThe positive rate of ADAs did not increase after switching from intravenous IFX to intravenous CT-P13. Among the patients with ADAs, a high level of RF was observed at baseline.

Safety and Effectiveness of Rituximab Biosimilar CT-P10 during Routine Clinical Practice: Final Analysis of a Post-Marketing Surveillance Study in the Republic of Korea

Introduction CT-P10 is a rituximab biosimilar approved by regulatory agencies in many countries including European Union[1], the United States[2], and the Republic of Korea[3]. This Korean post-marketing surveillance (PMS) study evaluated the safety and effectiveness of CT-P10 in the firstly approved indications in Korea: non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). In the CT-P10 development program, randomized controlled trials (RCTs) were conducted in RA and follicular lymphoma (FL). Therefore, the present PMS study would provide a comprehensive profile of CT-P10 in indications where approval was based on the extrapolation of comparative clinical data. Moreover, this study would address the real-world data of CT-P10 in patients with a range of comorbidities and taking various concomitant medications during routine clinical practice. Method This was a prospective, open-label, observational PMS study conducted at 27 centers in Korea during the surveillance period (16 November 2016-15 November 2020). Patients who received their first CT-P10 treatment per prescribing information were eligible for the study, regardless of previous treatment receiving other rituximab products. The objective was to investigate the type and frequency of unexpected adverse events (AEs), adverse drug reactions (ADRs), and serious AEs during a 1-year (NHL and CLL) or 24-week (RA and GPA/MPA) follow-up period after the first administration of CT-P10. Effectiveness was assessed by treating physicians according to the best overall response (BOR) during the study in NHL and CLL patients, Disease Activity Score in 28 joints (DAS28) score in RA patients, and Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) criteria in GPA/MPA patients following the first CT-P10 administration. Results The safety population was defined as patients who received ≥1 dose of CT-P10 and had ≥1 safety follow-up visit after the first CT-P10 administration, and comprised 677 patients (604 NHL, 16 CLL, 42 RA, 15 GPA/MPA). Among 604 NHL patients, 108 patients were diagnosed with FL and 496 patients had diffuse large B-cell lymphoma (DLBCL). 611 patients (549 NHL, 15 CLL, 32 RA, 15 GPA/MPA) were included in the effectiveness population, excluding 66 patients whose effectiveness results were not reported. Of 620 NHL or CLL patients, 424 (62.8%) experienced 1,717 AEs and 172 (27.7%) had ADRs (Table 1). The most common AE and ADR was nausea in NHL or CLL patients, reporting for 69 (11.1%) patients and 30 (4.8%) patients, respectively. Of 42 RA patients, 13 (31.0%) patients reported a total of 35 AEs. Eight ADRs occurred in 6 (14.3%) RA patients. 13 (86.7%) out of 15 GPA/MPA patients reported a total of 45 AEs. The most common AE was cough (3 [7.1%]) in RA patients and pneumonia (4 [26.7%]) in GPA/MPA patients, respectively. In NHL patients, the response rate was 96.7% (468/484) for rituximab-naïve patients and 50.8% (33/65) for switched patients (i.e. who had received other rituximab products before CT-P10 treatment) each (Table 2). All CLL patients were rituximab-naïve and responder. The response rate was 77.8% (7/9) for rituximab-naïve patients and 100.0% (23/23) for switched patients in RA population. In GPA/MPA patients, response rates were 38.5% (5/13) and 100.0% (2/2) for rituximab-naïve and switched patients, respectively. Conclusion This PMS study demonstrated that the safety findings of CT-P10 were consistent with the known safety profile of CT-P10 and other rituximab products in NHL, CLL, GPA, MPA and RA. In terms of effectiveness analyses, high response rates were observed across indications, providing pertinent information for the use of CT-P10 in routine clinical practice. Reference [1] European Medicines Agency. Truxima summary of product characteristics 2022 [2] US Food and Drug Administration. Highlights of prescribing information, Truxima (CT-P10). 2022 [3] Ministry of Food and Drug Safety. Biological products 2016 Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study.

BackgroundIntravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of infliximab [CT-P13] has recently been shown to be as effective as IV infliximab after two doses of IV induction in a randomised trial, but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching programme to SC CT-P13 in patients treated with IV infliximab.MethodsPatients on established maintenance IV infliximab, who switched to SC CT-P13, were included in this retrospective multicentre cohort study. Disease activity was monitored serially with the Harvey-Bradshaw Index [HBI] for Crohn’s disease [CD] and the Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis (UC) for up to 12 months at months 3, 6, and 12. Faecal calprotectin [FC] and C-reactive protein [CRP] were recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6, and 12 following switch. The primary outcome measure was treatment persistence at latest follow-up. Secondary outcome measures included infliximab pharmacokinetics [PK], safety, need for corticosteroid rescue therapy, and need for surgery.ResultsWe included 181 patients, of whom 115 [63.5%] had CD. The majority [72.4%] were on 8-weekly dosing of intravenous infliximab prior to switching, and more than half [59.1%] were on concomitant immunomodulatory therapy. The majority of patients (CD: 106, 92.2%; UC: 46, 76.7%; and IBD unclassified [IBD-U]: 5, 83.3%) were in clinical remission. Treatment persistence rate was high [n = 167, 92.3%] and only 14 patients [7.7%] stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6, or 12 months for HBI, SCCAI, CRP, or FC. Of the total cohort, 25 patients (13.8%) had perianal CD. Of these, only two patients [8%] had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia [EUA]. Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl [range 0.4-16] to 16.0 µg/dl [range 2.3-16, p <0.001] at 3 months. Serum levels stayed stable at 6 months [median 16 µg/dl, range 0.3-17.2] and 12 months [median 16 µg/dl, range 0.3-19.1, both p <0.001 compared with baseline]. Among the variables examined, only antibodies to infliximab [ATI] was associated with infliximab levels (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, p <0.001]. A total of 14 patients [7.7%] developed ATI; of these, nine [64.3%] were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI [p = 0.15]. In a subset of patients receiving escalated IV infliximab dosing frequency prior to switching, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high.ConclusionsAmong patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity, with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13, and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13.

The safety and clinical effectiveness of rapid infusion with CT-P10 in patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia: A retrospective non-interventional post-authorization safety study in Europe.

Rapid infusion (RI) of the rituximab biosimilar CT‐P10 is currently only an approved treatment regimen for the treatment of rheumatoid arthritis. Although both CT‐P10 and reference rituximab are known to be frequently administered using a RI regimen (≤90 min) in clinical practice, published data on the safety of RI of CT‐P10 in patients with NHL and CLL are limited. Hence, this study collected real‐world safety and effectiveness data on RI‐CT‐P10 from the medical records of 196 patients with NHL or CLL in 10 European centers, 6 months after the date of the first RI (index date); the infusion‐related reaction (IRR) rate was compared to previously published data. Ten percent (95% confidence interval 6%–15%; n = 20/196) of patients experienced an infusion‐related reaction (IRR) on day 1–2 post‐index, which was not significantly different (p = 0.45) to the IRR rate for rituximab described in a previous meta‐analysis (8.8%). During the observation period, 2% of patients experienced grade 3–5 IRRs and 85% (n = 166) experienced an adverse event (non‐IRR). The most common reason for discontinuation of first‐line CT‐P10 was planned treatment completion (81%; n = 158). Complete response and partial response to CT‐P10 was observed in 74% (n = 142/192) and 22% (n = 42/192) of patients, respectively. The results of this real‐world study demonstrate that the safety and effectiveness profile of RI‐CT‐P10 is similar to RI of reference rituximab and therefore support the current use of RI‐CT‐P10 in patients with NHL and CLL.

A Prospective Observational Study on the Efficacy and Safety of Infliximab-Biosimilar (CT-P13) in Patients With Takayasu Arteritis (TAKASIM).

Objectives: Infliximab (IFX) is widely used in patients with refractory Takayasu arteritis (TAK). Recently, the IFX-biosimilar CT-P13 has been introduced for the treatment of inflammatory diseases. The aim of this study was to assess the efficacy and safety of CT-P13 in patients with refractory TAK.Methods: In this prospective, open-label, single-center trial, TAK patients either already on treatment with IFX-originator (switch group) or never treated with IFX (naïve group) received CT-P13 for 52 weeks. The primary outcomes of the study were: (i) number of patients with active disease at month 6; (ii) incidence of treatment-emergent adverse events at month 12. Disease activity was assessed at month 6 and month 12 by clinical evaluation (ITAS-2020, ITAS-ESR, and ITAS-CRP scores) and imaging assessment [magnetic resonance angiography (MRA) and (18F)-FDG-PET].Results: 23 patients were recruited (21 switch, 2 naïve). At baseline, 7 patients (32%) were classified as active. At month 6, one patient voluntarily dropped out and 7 patients were still active (30%), including one patient started on a different bDMARD at month 2 due to poor disease control. Mean daily dose of prednisone equivalent was significantly lower than baseline (4.2 ± 1.9 mg vs. 4.8 ± 2.1 mg, p = 0.009). At month 12, another patient was excluded because of pregnancy desire. Five patients were classified as active (24%), including two patients started on a different bDMARD at month 2 and month 6. Mean daily dose of prednisone equivalent was significantly lower than baseline (3.3 ± 2.6, p = 0.034). No patient experienced side effects during CT-P13 infusion. Overall, one patient experienced grade 1 adverse event and 9 patients experienced grade 2 adverse events. In no case hospitalization was required. CT-P13 retention rate was 90.9% at month 6 and 90.4% at month 12.Conclusion: In this study, the use of IFX-biosimilar CT-P13 in patients with refractory TAK showed satisfying efficacy and safety profile.

P358 An observational, prospective cohort study to evaluate the long term safety and effectiveness of intravenous CT-P13 (biosimilar of infliximab) in patients with Crohn’s Disease or Ulcerative Colitis

Abstract Background CT-P13 is the world’s first approved biosimilar infliximab for all indications of the reference infliximab. The purpose of this study was to assess long term safety and effectiveness of CT-P13 intravenous (IV) in patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC). We now present the result of safety and effectiveness of CT-P13 in patient with CD, UC for up to 5 years from this longitudinal, observational, prospective cohort Phase IV study. Methods The study was conducted from 17 April 2014 to 28 February 2020 in 22 and 21 study centres, in Korea and European Union, respectively. Patients were administered 5 mg/kg of CT-P13 by IV at weeks 0, 2 and 6 and every 8 weeks thereafter. The primary objective was to evaluate adverse events of special interest (AESI) including HBV reactivation, congestive heart failure, opportunistic infections, serious infection including sepsis, tuberculosis, serum sickness (delayed hypersensitivity reactions), hematologic reactions, systemic lupus erythematosus/lupus like syndrome, demyelinating disorders, lymphoma, hepatobiliary events, hepatosplenic T cell lymphoma (HSTCL), intestinal or perianal abscess (in CD), serious infusion reactions during a re-induction regimen following disease flare, sarcoidosis/sarcoid-like reactions, paediatric malignancy, leukaemia, malignancy, colon carcinoma, dysplasia (in UC), skin cancer, pregnancy exposure and bowel stenosis, stricture and obstruction (in CD). Results A total of 470 patients with inflammatory bowel disease (IBD) were analysed. Overall 352 (74.9%) patients have been continuously treated for more than 1 year and the mean duration of drug exposure was 26.3 months. The safety profile of CT-P13 and switching from the reference infliximab to CT-P13 was well-tolerated. A total of 329 (70.0%) patients experienced at least one treatment-emergent adverse event (TEAE). Adverse events of special interest of CT-P13 were analysed by safety analysis set (Table 1). Immunogenicity testing was optional and 72 (15.3%) patients had at least one ADA positive after first infusion of study drug. The incidence of TEAEs in ADA positive subset (83.3%) were slightly higher compared to the incidence of TEAEs in ADA negative subset (76.6%). The effectiveness results of clinical remission for each indication was generally well maintained after the study drug administration (Table 2). Conclusion The results show that CT-P13 was well-tolerated and efficacious in IBD patients. There was no new safety and effectiveness findings in patients who have been exposed to CT-P13 or patients who have switched treatment from the reference infliximab to CT-P13.

P344 Effectiveness and safety of switching patients with inflammatory bowel disease from originator infliximab to CT-P13: systematic review and meta-analysis

Abstract Background Switching from originator infliximab (IFX) to the CT-P13 biosimilar is a widespread practice, although some concerns persist, particularly about long-term outcomes. We performed a systematic review and meta-analysis to assess the effectiveness and safety of switching from originator IFX to CT-P13 in patients with inflammatory bowel disease (IBD). Methods We systematically searched electronic databases for randomised controlled trials and prospective observational studies of adult patients with IBD who had switched from originator IFX to CT-P13 and were followed up for at least 12 months. The main outcomes were the pooled rate of clinical remission (as defined by the included studies) and adverse events at 12 months. Secondary outcomes included the rate of treatment discontinuation and de novo immunogenicity. A DerSimonian-Laird random-effects meta-analysis of proportions with double arcsine transformation was performed. Variables judged to be clinically important were studied in an exploratory random-effects meta-regression analysis. Results Eleven studies with 1204 patients (71% with Crohn’s disease [CD]) switching from originator IFX to CT-P13 were identified. Pooled rates of clinical remission at 12 months were 83.6% in ulcerative colitis (UC), 75.9% in CD, and 79.6% in mixed cohorts (Figure 1). Clinical remission at 12 months was negatively associated with combined immunosuppression at switch (7% decrease in remission at 12 months per 10% increase in patients receiving combination therapy) and positively associated with remission at switch (6% increase in remission at 12 months per 10% increase in remission at switch). The pooled rate of adverse events at 12 months was 21.0% (95% confidence interval [CI] 10.4–34.1%). Pooled rates of treatment discontinuation at 12 months were 24.4% (95% CI 12.0–39.4%) in UC, 18.6% (95% CI 8.8–30.9%) in CD, and 13.1% (95% CI 0.7–35.6%) in mixed cohorts. De novo immunogenicity was rare (3.3%, 95% CI 1.5–5.6%). All estimates had at least moderate heterogeneity. Figure 1: Meta-analysis of clinical remission rates at 12 months after switching from originator infliximab to CT-P13 in ulcerative colitis and Crohn’s disease. Conclusion Switching from originator IFX to CT-P13 appears to be effective and safe, although these findings should be interpreted in the context of the limitations of the primary publications which lacked control arms. Combined immunosuppression at switch, potentially as a marker of disease severity, was negatively associated with clinical remission at 12 months after the switch.

Long-Term Efficacy and Safety (27 months) of the Biosimilar CT-P10 in Patients with Low Tumor Burden Follicular Lymphoma

We assessed long-term safety and efficacy of CT-P10 and rituximab in patients with newly diagnosed low-tumour-burden follicular lymphoma (LTBFL), and following a single transition from rituximab to CT-P10. This double-blind, parallel-group, active-controlled phase 3 trial randomized patients with CD20+ LTBFL to receive CT-P10 or US-sourced rituximab (375 mg/m2 intravenous). Induction therapy (weekly for 4 cycles) was followed by a 2-year maintenance period for patients achieving disease control (CR, CRu, PR and SD). During the maintenance, CT-P10 or rituximab were administered every 8 weeks (6 cycles) in the first year and additional CT-P10 was administered every 8 weeks (6 cycles) in the second year. Secondary endpoints (reported here) were overall response rate during the study period, progression-free survival, time-to-progression, and overall survival. Safety and immunogenicity were also evaluated over the study period. Between Nov 9, 2015 and Jan 4, 2018, 258 patients were randomised (130 CT-P10; 128 rituximab). Over the study period, 115 (88%; CT-P10) and 111 (87%; rituximab) patients achieved overall response. At a median follow-up of 29·2 months (IQR: 26·1-33·7), median progression-free survival, time-to-progression, and overall survival were not estimable. The KM estimates (95% CI) for OS at 36 months were 98% (93-99) and 97% (89-99) in the CT-P10 and rituximab groups, respectively. Corresponding values for PFS were 80% (70-87) and 68% (54-79), while results for TTP were 82% (72-88) and 68% (54-79) in the CT-P10 and rituximab groups, respectively. (Figure A. OS; Figure B. PFS and Figure C. TTP) Over the study period, 114 (88%) and 104 (81%) patients in the CT-P10 and rituximab groups, respectively, experienced at least one treatment-emergent adverse event (TEAE) and 14 (11%) patients in each group experienced TE-serious adverse events (TESAEs). There were no unexpected safety findings observed during the second year of the maintenance period after single transition from rituximab to CT-P10. Figure 1 Disclosures Kwak: Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees; Xeme Biopharma/Theratest: Other: equity; CJ Healthcare: Consultancy; Sellas Life Sciences Grp: Consultancy; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; InnoLifes, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pepromene Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy. Sancho:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Gelgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Menne:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Other: Travel costs, Speakers Bureau; Pfizer: Honoraria, Other: Travel costs, Speakers Bureau; Celgene: Honoraria, Other: Travel grants; Roche: Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Research Funding; Takeda: Honoraria, Speakers Bureau. Jurczak:Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Acerta: Research Funding; Bayer: Research Funding; Janssen: Research Funding; MeiPharma: Research Funding; Pharmacyclics: Research Funding; Roche: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. Trneny:Gilead: Consultancy, Honoraria, Other: Travel Expenses; Janssen: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Celgene: Consultancy; Incyte: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses. Ogura:Cellgene: Honoraria; Chugai: Honoraria; Denovo Biopharma: Membership on an entity's Board of Directors or advisory committees; MejiSeika Pharma: Membership on an entity's Board of Directors or advisory committees; Mundi Pharma: Membership on an entity's Board of Directors or advisory committees; SymBio: Membership on an entity's Board of Directors or advisory committees; TevaTakeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Membership on an entity's Board of Directors or advisory committees. Kim:Pfizer: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; F. Hoffmann-La Roche: Research Funding; Kyowa Kirn: Research Funding; Celltrion: Research Funding; JJ: Research Funding. Lee:Celltrion, Inc.: Current Employment. Kim:Celltrion, Inc.: Current Employment. Ahn:Celltrion, Inc.: Current Employment. Buske:Roche, Janssen, Bayer, MSD: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen, AbbVie, Pfizer, Celltrion: Honoraria, Speakers Bureau. OffLabel Disclosure: Rituximab monotherapy to LTBFL patients

A 5-year Retrospective Analysis of Drug Survival, Safety, and Effectiveness of the Infliximab Biosimilar CT-P13 in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.

The infliximab biosimilar CT-P13 has widely received regulatory approval in all indications of reference infliximab, including rheumatoid arthritis (RA) and ankylosing spondylitis (AS). This retrospective analysis investigated drug survival and long-term safety and effectiveness of CT-P13 in patients with RA or AS in the Republic of Korea. This non-interventional, retrospective, multicenter analysis collected medical record data for adult patients with RA or AS who received CT-P13 treatment at five Korean referral hospitals (2012-2017). Drug survival and long-term safety were primary outcomes. The secondary outcome was long-term effectiveness, assessed by disease activity measures. Overall, 491 patients were treated with CT-P13 (154 patients with RA [135 infliximab-naïve; 19 switched from reference infliximab]; 337 patients with AS [219 infliximab-naïve; 118 switched from reference infliximab]). Drug survival was similar in naïve and switched patients. Treatment-emergent adverse events (TEAEs) occurred in 31.8% and 29.4% of patients with RA and AS, respectively; incidence was similar in naïve and switched groups. Upper respiratory tract infection, influenza-like illness, and urticaria were the most common TEAEs. Overall, nine (1.8%) patients experienced serious adverse events (SAEs) deemed potentially drug-related; SAEs led to permanent CT-P13 discontinuation in five (1.0%) patients, including three with tuberculosis. Disease activity decreased over time. Up to 5years of CT-P13 treatment was safe and effective in patients with RA and AS, basedon drug survival, incidence of TEAEs, and disease activity. Drug survival and safety were similar in naïve patients and switched groups, supporting switching from reference infliximab to CT-P13.

P326 Reasons for and effectiveness of switching back to originator infliximab after a prior switch to CT-P13 biosimilar

Abstract Background In current clinical practice, patients with inflammatory bowel disease (IBD) treated with originator infliximab (IFX) have been or are being switched to biosimilar infliximab (CT-P13) because of lower costs and seemingly similar effectiveness of biosimilars. Over a one-year follow-up, 7%-26% of the patients discontinue CT-P13 treatment. Common reasons for CT-P13 discontinuation are (subjective) loss of response or adverse events. As a result of these newly experienced symptoms, patients are occasionally switched back to treatment with originator IFX. However, not much is currently known regarding reverse switching to originator IFX. We aimed to assess the prevalence of and the specific reasons for reverse switching to originator infliximab within 52-weeks after an initial conversion from originator infliximab to CT-P13 in patients with IBD. Additionally, we evaluated whether reinitiating originator infliximab led to the desired favourable effect and sustained infliximab use. Methods In this retrospective, multicentre cohort study, data of IBD patients from eight hospitals in the Netherlands were collected. Adult patients with IBD were eligible for inclusion if they were switched from infliximab originator to CT-P13 and had a follow-up time of at least 52 weeks after initial conversion. Reasons for re-switching were categorised into adverse events or loss of response on the biosimilar. Drug survival was analysed with a time-varying Cox proportional hazards model. Results A total of 684 patients with IBD were switched (516 Crohn’s disease, 168 ulcerative colitis). Reverse switching was seen in 74 (10.8%) patients after a median of 140 days (IQR 86–231). Reverse switchers were more often females (70.3% vs. 49.7%, p &amp;lt; 0.001) and had shorter originator treatment (4.0 [IQR 2.6–6.5] vs. 5.2 [IQR 3.0–7.5] years, p = 0.037) than those who stayed on CT-P13. A total of 105 symptoms for switching were reported. IBD-like symptoms (25.7%) and dermatological symptoms (21.9%) were the most common. Four patients had objectified loss of response. All regained response after switching back. IBD-like symptoms and dermatological symptoms were reversible in 74.1% and 87%, respectively. Overall reversibility of symptoms was 73.3%. Cox proportional hazards model with CT-P13/originator infliximab as time-varying covariate, yielded no difference in survival risk (hazard ratio 1.23, 95% CI 0.65–2.33). Conclusion Switching back to originator infliximab seems effective in patients with IBD, who experience adverse effects or loss of response after switching from originator to CT-P13. Switching patients back to originator infliximab might, therefore, be justified in case patients experience new side effects or loss of response after switching to CT-P13.

Real-world use of therapeutic drug monitoring of CT-P13 in patients with inflammatory bowel disease: A 12-month prospective observational cohort study

Whether therapeutic drug monitoring (TDM) of infliximab should be implemented in daily practice is an ongoing controversy. To assess the real-world use of TDM in an observational multicentre cohort study with consecutive patients with inflammatory bowel disease (IBD) treated with CT-P13. Between September 2015 and December 2016, 364 patients with IBD were treated with CT-P13 in 13 gastroenterology departments and were followed up for 54 weeks. Disease activity, CT-P13 trough concentration and anti-CT-P13 antibody (ACA) were recorded. Steroid-free clinical remission rates at week 54 were 67.0% and 56.4% in patients with CD and UC, respectively. CT-P13 trough concentrations were measured in 70.7% of the patients. The mean CT-P13 trough concentration was 4.2±4.3μg/mL. The presence of ACA was observed in 53 (15.9%) patients. CT-P13 trough concentration was collected in a proactive approach in 62.8% of cases and in a reactive approach in 37.2%. Among patients who submitted to TDM, CT-P13 therapy was optimized in 88.7% of the reactive group and in 22.5% of the proactive group (P<0.001). In a real-world cohort of patients with IBD treated with CT-P13, more than two-thirds of the patients underwent TDM. CT-P13 optimization was much less common in the proactive approach than in the reactive approach.

Comparative Effectiveness of Certolizumab Pegol, Abatacept, and Biosimilar Infliximab in Patients With Rheumatoid Arthritis Treated in Routine Care: Observational Data From the Danish DANBIO Registry Emulating a Randomized Trial.

Nationwide Danish guidelines regarding rheumatoid arthritis (RA) patients initiating biologic treatment (i.e., biologic disease-modifying antirheumatic drugs [DMARDs]) are issued on an approximately annual basis. For biologics-naive patients treated with concomitant methotrexate, mandatory medications included certolizumab pegol (CZP; year 2013-2014, recommended compliance 80%), abatacept (ABA; 2014-2015, 80%), and biosimilar infliximab (CT-P13; 2015-2016, 50%). We hypothesized that these guidelines could be perceived as a surrogate randomization tool in which calendar period rather than patient-specific factors defined the choice of the biologic DMARD. We undertook this study to assess compliance with guidelines (supporting the assumption of surrogate randomization) and to compare the effectiveness of CZP, ABA, and CT-P13 in patients treated according to guidelines. This was an observational cohort study emulating a randomized trial (using intent-to-treat analyses). RA patients compliant with the treatment guidelines were identified in DANBIO, and information on prior comorbidities was obtained by linking to national registries. Outcome measures included remission rates according to the Disease Activity Score in 28 joints (DAS28) (at 6 and 12 months) and treatment retention at 1 year, compared across treatment regimens. Comorbidity/confounder-adjusted multivariable logistic and Cox regression analyses were used. Seven hundred seventy-six patients were included in the study (336 receiving CZP, 215 receiving ABA, 225 receiving CT-P13). Compliance with treatment guidelines was high: 70%, 65%, and 59%, respectively. Six-month DAS28 remission rates were 35%, 33%, and 42%, and 12-month rates were 35%, 31%, and 35%, respectively. Compared to CZP, adjusted odds ratios for 6- and 12-month DAS28 remission rates were 0.96 (95% confidence interval [95% CI] 0.63-1.47) and 0.74 (95% CI 0.47-1.15) for ABA and 1.38 (95% CI 0.91-2.09) and 0.96 (95% CI 0.62-1.49) for CT-P13, respectively. Adjusted hazard ratios for withdrawal (during days 0-90 and days 91-365) were 0.70 (95% CI 0.39-1.27) and 1.16 (95% CI 0.84-1.60) for ABA and 0.58 (95% CI 0.33-1.10) and 0.83 (95% CI 0.59-1.17) for CT-P13, respectively, compared to CZP. The surrogate randomization procedure enabled head-to-head comparisons of CZP, ABA, and CT-P13. Although some differences in estimated effectiveness were observed across drugs, confidence intervals were wide and statistical significance was not reached.

Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study

Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study

Patients’ perspectives after switching from infliximab to biosimilar CT-P13 in patients with inflammatory bowel disease: A 12-month prospective cohort study

BackgroundPatients’ perspectives after switching from infliximab to a biosimilar have yet to be assessed. AimTo assess patients’ perspectives in a prospective manner after switching from infliximab to CT-P13. Methods113 consecutive patients with inflammatory bowel disease (IBD) on maintenance therapy with infliximab were switched to CT-P13. Patients’ perspectives were assessed by questionnaires, including the Beliefs about Medicines Questionnaire (BMQ) and FACIT-F (questionnaire regarding fatigue), and patient-reported outcomes (IBD disability index) at the inclusion and after the fourth CT-P13 infusion. ResultsAfter one year, the patients’ perspectives did not change after the switch according to BMQ-general, BMQ-specific necessity and BMQ-specific concerns subscales. No difference was observed in the mean IBD-DI score, while a significant improvement in fatigue was observed according to the FACIT-F questionnaire. Patients’ concerns were raised about the use of biosimilars and the risks of switching with a significant improvement after switching (65% vs. 42%, respectively, p = 0.01). Fourteen (12.4%) patients experienced loss of response to CT-P13, including 12 with restoration of steroid-free clinical remission after CT-P13 dose optimization. ConclusionAlthough some concerns were reported, no difference was observed in patients’ perspectives after switching from infliximab to CT-P13.

Retention rate and long-term safety of biosimilar CT-P13 in patients with ankylosing spondylitis: data from the Korean College of Rheumatology Biologics registry

To evaluate the long-term drug retention, efficacy, and safety of the infliximab biosimilar CT-P13 in Korean patients with ankylosing spondylitis (AS) in clinical practice. The primary outcome was drug retention (i.e. time to treatment discontinuation or changing to another biologic) in Korean patients with AS. Additional outcomes included efficacy and safety. Data were collected through the Korean College of Rheumatology Biologics (KOBIO) registry (ClinicalTrials.gov identifier: NCT01965132). CT-P13 efficacy was assessed using standard disease activity parameters, and safety was evaluated by adverse events (AEs). Between December 2012 and December 2017, 244 patients with AS treated with CT-P13 were enrolled. Of those, 203 (83.2%) received CT-P13 as first-line therapy. The median duration of treatment was 2.05 years. After 4 years' follow-up, the retention rate of CT-P13 in the overall patient population was 66%. Treatment changes or discontinuations occurred in 38 (15.6%) and 32 (13.1%) patients, respectively. Lack of efficacy was the most common reason for treatment changes, whereas AEs were the most common single cause of discontinuation. Disease activity decreased markedly from baseline following initiation of CT-P13 treatment, and thereafter remained stable. A total of 313 AEs occurred in 118 patients (48.4%); the majority (94.6%) were mild or moderate in severity. The most common treatment-related AEs were infusion or injection-site reactions (4.1% of patients), uveitis (3.7%), and skin rash (3.7%). In this real-world study, CT-P13 demonstrated encouraging drug retention rates and times, together with reasonable long-term efficacy and safety, in Korean patients with AS.

PF314 REAL WORLD CLINICAL EFFECTIVENESS AND SAFETY OF CT-P10 IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA: INTERIM RESULTS FROM A EUROPEAN NON-INTERVENTIONAL POST-AUTHORISATION SAFETY STUDY

Background: In February 2017, CT-P10 became the first biosimilar of rituximab to be approved in Europe for treatment of rheumatic diseases and specific blood cancers including non-Hodgkin's lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the commonest type of NHL, representing an estimated 40–58% of cases (Sant et al, 2010). To date, no studies have investigated the effectiveness or safety of CT-P10 in patients with DLBCL in the real world clinical setting. Aims: To evaluate the real world clinical effectiveness and safety of CT-P10 in patients with DLBCL in Europe. Methods: This non-interventional post-authorisation safety study is in progress in five European countries (France, Germany, Italy, Spain and the United Kingdom [UK]), and involves collection of data from the medical records of consenting adult patients with DLBCL who were treated with CT-P10 as part of their routine clinical care. Effectiveness and safety data are being collected for an observation period of 30 months after the index date (date of CT-P10 initiation) or until death, if sooner. The primary objective is to describe the effectiveness of CT-P10 (overall survival, progression free survival, CT-P10 responses), with secondary objectives to describe the safety profile and CT-P10 treatment pathways. Response to CT-P10 is as documented by the local investigator. Here we report interim results (patients’ baseline characteristics and preliminary response/safety data), based on a data cut on 18 January 2019. Where n is less than the total number of patients, data were missing. Results: The interim analysis includes 151 patients enrolled from sites in the UK and Spain, with a median 8.9 months (interquartile range [IQR] 6.1–12.6) post-index observation at the cut-off. Patients are receiving CT-P10 as a first-line (n = 138, 91%), second-line (n = 9, 6%) or third-line (n = 4, 3%) DLBCL treatment. Ninety-five (63%) patients are male. Other patient characteristics at index: median age 70.9 years (IQR 61.5–76.0) (n = 149); median disease duration 20 days (IQR 10.5–41.0) (n = 147); Eastern Cooperative Oncology Group performance status (n = 98): 0 (n = 45, 46%), 1 (n = 36, 37%), 2 (n = 11, 11%), 3 (n = 4, 4%) or 4 (n = 2, 2%); Ann Arbor stage (n = 77): I (n = 8, 10%), II (n = 9, 11%), III (n = 18, 21%), IV (n = 40, 48%) or other (n = 2, 2%; recorded as ‘at least stage II’). Best responses to CT-P10 (evaluable in n = 128) are shown in Fig. 1. Safety of CT-P10 was evaluable in 128 patients, of whom 118 (92%) experienced adverse events (AEs) during the observation period (732 AEs recorded in total, including infusion-related reactions), 77 (60%) had AEs of grade 3 and above and 11 (9%) discontinued CT-P10 due to AEs.Summary/Conclusion: Early results from this ongoing study suggest that a high proportion of patients with DLBCL treated with CT-P10 in the real world achieve complete or partial responses, similar to the response rates reported previously for reference rituximab (Horvat et al, 2017). Continued recruitment and extended follow-up will enable more comprehensive analyses of CT-P10 effectiveness and safety.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.