Results from the open-label extension of NOR-SWITCH, a randomized switching trial in Norway

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1 Results from the open-label extension of NOR-SWITCH, a randomized switching trial in Norway LIS-møte, Trondheim 21 mars 2018 Guro Løvik Goll MD PhD Kristin Kaasen Jørgensen MD PhD On behalf of the NOR-SWITCH study group

2 Disclosures Dr Guro Løvik Goll has received honoraria and/or served as consultant for AbbVie, Boehringer Ingelheim, Novartis, Pfizer, Orion Pharma, Eli Lilly, Roche, Celltrion and Sandoz Dr Kristin K Jørgensen has received honoraria and/or served as consultant for Intercept, Celltrion, Tillotts, Sandoz and MSD The NOR-SWITCH study was funded by the Norwegian Ministry for Health and Care services

3 Jørgensen KK, Olsen IC, Goll GL, et al. Lancet 2017; 389:

4 Nor-Switch study design Randomisation 1:1 Primary endpoint: disease worsening Maintenance treatment with originator IFX IFX CT-P13 SWITCH GROUP (CT-P13) MAINTENANCE GROUP (CT-P13) N=482 N=380 Intervention period Open label follow-up W 0 W 52 W 78

5 Disease worsening definitions Primary endpoint: Worsening definition RA and PsA AS/SpA UC CD Psoriasis ΔDAS min. score: 3.2 ΔASDAS 1.1 min score:2.1 ΔpMayo 3 min score: 5 ΔHBI 4 min score:7 ΔPASI 3 min score: 5 Occurrence of disease worsening during the 52-week study period based on disease specific efficacy assessment scores Patient and investigator consensus on disease worsening If a patient does not fulfill the formal definition, but experiences a clinically significant worsening according to both the investigator and patient and which leads to a major change in treatment

6 Nor-Switch: disease worsening Jørgensen KK, Olsen IC, Goll GL, et al. Lancet 2017; 389:

7 Single-transition trial designs orner2015/figure4 bbers2014/figure1 Reference drug Biosimilar Biosimilar NOR-SWITCH extension, PLANETRA open-label extension, PLANETAS open-label extension, SB4 open-label extension Open-label transition study No data on patients switched from biosimilar to reference drug No data on the outcomes of more than one switchn comparison of switching versus continuous treatment with reference drug Reference drug Randomize NOR-SWITCH main trial RCT, randomised controlled trial. Reference drug Biosimilar Randomized transition study Strengths: Double-blind comparison of a single-direction switch from reference product to biosimilar versus continuous treatment with reference Weaknesses: No data on patients switched from biosimilar to reference drug No data on the outcomes of more than one switch Adapted from Dörner et al 2015

8 Results from the open-label extension study

9 NOR-SWITCH trial (52-weeks) 482 randomised 241 switch to CT-P continued treatment with INX Discontinued (n=19) Discontinued (n=25) 222 completed 216 completed Did not enter extension Study (n=25) Did not enter extension Study (n=33) NOR-SWITCH EXTENSION trial (26 weeks) Discontinued (n=7) 197 Maintenance group (CT-P13 continued) Full Analysis Set 190 completed Per Protocol Set 183 Switch group (switch to CT-P13) Full Analysis Set 173 completed Per Protocol Set Discontinued (n=10)

10 Distribution of diagnoses, extension N= 380 (FAS)

11 Data are n (%), mean (SD) or median (IQR). *Immunosuppressive concomitant medication includes methotrexate, leflunomide, sulfasalazine, azathioprine, and mercaptopurine RA rheumatoid arthritis, PsA psoriatic arthritis SpA spondyloarthritis. Demographics and baseline characteristics at 52w (FAS) CT-P13/CT-P13 group (n=197) INX/CT-P13 group (n=183) Age (years) 48.8 (14.9) 48 (14.3) Females 64 (33%) 78 (43%) Disease duration (years) 18.1 (10.6) 17.3 (10.4) Duration of ongoing IFX treatment (years) 7.7 (3.8) 7.4 (3.5) Concomitant immunosuppressive therapy* 106 (54%) 85 (46%) Erythrocyte sedimentation rate (mm/h) 8 (4-17) 7 (4-15) C-reactive protein (mg/l) 2 (1-5) 2 (1-5) DAS 28 (RA) 2.4 (0.9) 2.8 (0.9) DAS28 (PsA) 2.1 (1.1) 2.9 (1.8) BASDAI (SpA) 3.2 (1.8) 2.6 (1.6) ASDAS (SpA) 1.9 (0.8) 1.7 (0.7) Harvey Bradshaw Index (CD) 1 (0-4) 1 (0.2-4) Partial Mayo Score (UC) 0 (0-0) 0 (0-1) Psoriasis Area and Severity Index (Pso) 2.1 (1.4) 1.3 (1.2)

12 Nor-Switch Extension: disease worsening Maintenance group: CT-P13 throughout study period Switch group: INX main study period, switched to CT-P13

13 Disease specific composite measures HBI CDAI p-mayo score SDAI ASDAS PASI DAS28 Δ-Δ CTP-13/CT-P13 Ο-Δ INX/CT-P13

14 Trough drug levels

15 Treatment emergent adverse events Overview CT-P13/CT-P13 group (n=197) INX/CT-P13 group (n=183) Serious adverse events 17/14 (7%) 9/8 (4%) Adverse events 145/87 (44%) 118/74 (40%) Adverse events leading to study drug discontinuation 2 (1%) 1 (0.5%) Most frequent treatment emerging adverse events Infections 34/33 (17%) 16/15 (8%) Rash 3/3 (2%) 4/3 (2%) Elevated liver enzymes 3/2 (1%) 3/2 (1%) Iron deficiency 4/3 (2%) 2/1 (1%) Infusion related reaction 3/3 (2%) 2/2 (1%) Data are number of events/number of patients (%) in the Safety Population

16 Explorative subgroup-analyses in IBD in the NOR-SWITCH EXTENSION trial

17 Nor-Switch Main Study: disease worsening Jørgensen KK, Olsen IC, Goll GL, et al. Lancet 2017; 389:

18 Nor-Switch Main Study: sec. endpoints in IBD Crohn s disease Ulcerative colitis Harvey-Bradshaw index Fecal calprotectin Partial Mayo score Fecal calprotectin Trough drug levels Trough drug levels

19 Demographics and baseline characteristics in IBD (w 52) Crohn s disease Maintenance group (n=65) Switch group (n=62) Ulcerative colitis Maintenance group (n=42) Switch group (n=38) Age (years) 40 (13.9) 40 (13.1) 47 (14.7) 46 (13.4) Female 22 (34%) 27 (44%) 12 (29%) 14 (37%) Previous biologic naive 53 (82%) 49 (79%) 40 (95%) 37 (97%) Disease duration (years) 16 (8.8) 15 (9.1) 13 (7.5) 14 (9.5) Harvey-Bradshaw index 1 (0-4) 1 (0.2-4) - - Partial Mayo score (0-0) 0 (0-1) Faecal calprotectin (mg/kg) 183 (48-390) 68 (25-271) 29 (19-102) 46 (15-116) C-reactive protein (mg/l) 1.6 (1-5) 2.1 (1-4.5) 2 (1-5) 1.9 (1-3.8) EQ-5D Index score 0.8 (0.2) 0.8 (0.3) 0.9 (0.2) 0.9 (0.1) Data are n (%), mean (SD) or median (IQR)

20 Nor-Switch Extension: disease worsening Maintenance group: CT-P13 throughout study period Switch group: INX main study period, switched to CT-P13

21 Secondary endpoints in Crohn s disease CRP Patient s global assessment Calprotectin Physician s global assessment Se-IFX Δ-Δ CTP-13 CT-P13 Ο-Δ IFX CT-P13

22 Secondary endpoints in ulcerative colitis CRP Patient s global assessment Calprotectin Physician s global assessment Se-IFX Δ-Δ CTP-13 CT-P13 Ο-Δ IFX CT-P13

23 Treatment emergent adverse events in IBD Crohn s disease Ulcerative colitis Maintenance group (n=65) Switch group (n=62) Maintenance group (n=42) Switch group (n=38) Overview Serious adverse events 7/6 (9%) 4/3 (5%) 0 2/2 (5%) Adverse events 42/24 (37%) 28/18 (29%) 17/12 (29%) 20/14 (37%) Most frequent treatment emerging adverse events Infections 8/8 (12%) 3/3 (5%) 7/6 (14%) 8/8 (21%) Iron deficiency 3/2 (3%) 2/1 (2%) 0 0 Infusion related reaction 3/3 (5%) Kidney stones 1/1 (2%) 2/1 (2%) 0 0 Eczema 0 2/2 (3%) 0 0 Nausea 1/1 (2%) 1/1 (2%) 0 0 Rash 1/1 (2%) 1/1 (2%) 0 0 Back pain 1/1 (2%) 1/1 (3%) Data are number of events/number of patients (%) in the Safety Population

24 Conclusion I Short versus long-term treatment with CT-P13 is comparable regarding efficacy and tolerability. Explorative subgroup analyses of CD and UC demonstrates similarity between patients switching from IFX to CT-P13 and patients on long-term CT-P13 treatment. The results support switching from INX to CT-P13 for non-medical reasons

25 Conclusion II We recommend caution in generalizing these findings to other biologic agents Further studies are needed to examine reverse and cross-switching involving originator and biosimilar biologics

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