Comparison of brodalumab versus placebo at weeks 16 and 24 using generalised estimating equation
| Response, % | AMVISION-1 | AMVISION-2 | Pooled | ||||||
| PBO | BRO 140 mg Q2W | BRO 210 mg Q2W | PBO | BRO 140 mg Q2W | BRO 210 mg Q2W | PBO | BRO 140 mg Q2W | BRO 210 mg Q2W | |
| Week 16 | |||||||||
| ACR20 | 16.0 | 39.5† | 51.8† | 24.8 | 50.9† | 44.3*** | 20.9 | 45.8† | 47.9† |
| ACR50 | 4.6 | 18.3*** | 28.8† | 9.1 | 29.3† | 23.2** | 7.2 | 24.8† | 26.1† |
| ACR70 | 2.7 | 7.8 | 12.5** | 3.6 | 13.3** | 10.2* | 3.4 | 11.3*** | 12.2*** |
| PASI75 | 10.9 | 55.0† | 81.1† | 9.3 | 51.5† | 70.5† | 10.4 | 52.4† | 75.5† |
| PASI90 | 7.3 | 44.0† | 69.0† | 5.1 | 35.0† | 49.3† | 6.1 | 38.5† | 58.8† |
| PASI100 | 4.3 | 21.2*** | 49.6† | 3.0 | 18.3*** | 34.1† | 3.9 | 20.7† | 40.8† |
| Dactylitis resolution | 17.3 | 31.3 | 48.8*** | 29.7 | 49.6* | 53.4** | 24.2 | 40.9** | 50.8† |
| Enthesitis resolution | 16.0 | 34.2* | 37.8** | 28.9 | 48.5* | 39.6 | 23.7 | 42.3*** | 39.1** |
| HAQ-DI LS mean change from baseline‡ | –0.136 | –0.346*** | –0.439† | –0.161 | –0.299** | –0.325** | –0.154 | –0.321† | –0.385† |
| Achievement of HAQ-DI MID§ | 25.0 | 42.6** | 59.1† | 34.6 | 51.6** | 53.8** | 30.3 | 47.5*** | 56.1† |
| DAS28 CRP LS mean change from baseline‡ | –0.203 | –1.075† | –1.299† | –0.324 | –1.148† | –1.086† | –0.269 | –1.115† | –1.189† |
| CDAI LS mean change from baseline‡ | –1.981 | –12.03† | –12.61† | –4.153 | –12.05† | –11.53† | –3.325 | –12.01† | –12.04† |
| DAPSA LS mean change from baseline‡ | 0.068 | –18.73*** | –18.96*** | –5.142 | –16.41*** | –16.22*** | –3.152 | –17.51*** | –17.61*** |
| PASDAS LS mean change from baseline‡ | –0.163 | –1.578*** | –2.120*** | –0.434 | –1.474*** | –1.725*** | –0.325 | –1.526*** | –1.913*** |
| Week 24 | |||||||||
| ACR20 | 18.9 | 52.2† | 59.7† | 27.8 | 49.5*** | 48.8*** | 23.8 | 51.0† | 53.6† |
| ACR50 | 8.0 | 26.8*** | 37.5† | 11.9 | 31.2*** | 35.4† | 10.4 | 29.8† | 36.4† |
| ACR70 | 2.5 | 11.2** | 20.0† | 6.1 | 15.7* | 19.2** | 4.7 | 14.4*** | 20.9† |
| PASI75 | 9.4 | 51.4† | 80.7† | 8.9 | 49.0† | 62.3† | 9.6 | 50.5† | 70.5† |
| PASI90 | 3.8 | 42.2† | 61.8† | 3.8 | 32.3† | 52.0† | 3.8 | 36.6† | 57.1† |
| PASI100 | 3.5 | 26.8*** | 52.0† | 0.7 | 23.5** | 45.5*** | 1.9 | 26.0† | 48.6† |
| Dactylitis resolution | 14.0 | 26.4 | 59.4† | 22.9 | 59.5*** | 60.0*** | 19.8 | 43.0*** | 60.1† |
| Enthesitis resolution | 15.7 | 33.8* | 54.8† | 27.3 | 47.2* | 37.8 | 22.7 | 41.6** | 43.8*** |
| HAQ-DI LS mean change from baseline‡ | –0.192 | –0.411** | –0.526† | –0.226 | –0.332 | –0.398** | –0.216 | –0.371** | –0.467† |
| Achievement of HAQ-DI MID§ | 23.5 | 44.4** | 60.9† | 28.9 | 47.5** | 49.6** | 26.3 | 46.1† | 54.3† |
| DAS28 CRP LS mean change from baseline‡ | –0.682 | –1.348** | –1.734† | –0.714 | –1.233** | –1.276** | –0.698 | –1.275† | –1.495† |
| CDAI LS mean change from baseline‡ | –7.086 | –14.64† | –16.38† | –8.778 | –12.67* | –13.36** | –8.153 | –13.53† | –14.87† |
| DAPSA LS mean change from baseline‡ | –6.797 | –21.97*** | –25.68*** | –11.75 | –17.28* | –19.25** | –10.12 | –19.53*** | –22.46*** |
| PASDAS LS mean change from baseline‡ | –0.636 | –1.981*** | –2.599*** | –0.857 | –1.810*** | –2.155*** | –0.778 | –1.892*** | –2.369*** |
Full analysis set. Response rates were calculated using a GEE model. NRI was applied following early withdrawal from trial for reasons other than premature trial termination, and to subjects who satisfied the inadequate response criteria prior to week 24. GEE analysis assumed missing data due to early trial termination and intermittent missing data were missing completely at random. Patient numbers are reported in online supplemental table 1.
ACR responses were modified based on 66/68 joint counts. PASI responses were calculated using the psoriasis efficacy full analysis set (patients with baseline BSA ≥3%). Dactylitis and enthesitis responses were evaluated in patients with these conditions at baseline. Dactylitis was assessed as present (yes/no) on 20 digits (fingers and toes). Enthesitis was assessed as present (yes/no) on six entheses (lateral epicondyle, medial femoral condyle and Achilles tendon insertion).
*p<0.05 versus placebo; **p<0.01 versus placebo; ***p<0.001 versus placebo; †p<0.0001 versus placebo.
‡Change in LS mean values from baseline. p values shown are calculated for the LS mean difference versus placebo. The estimates are calculated as active treatment minus placebo using a linear mixed-effects model for repeated measures. A reduction indicates a beneficial treatment effect. The model contains visit, treatment, treatment by visit and baseline by visit interaction, baseline and three randomisation strata: baseline weight (≤100 kg, >100 kg), prior biologic use (yes/no) and geographical region (North and Latin America, Central/Eastern Europe, Western Europe).
§The MID used for HAQ-DI in PsA is 0.35.15
ACR20/50/70, American College of Rheumatology 20/50/70% improvement criteria; BRO, brodalumab; BSA, body surface area; CDAI, Clinical Disease Activity Index; CRP, C reactive protein; DAPSA, Disease Activity in Psoriatic Arthritis; DAS28, Disease Activity Score with a 28-joint count; GEE, generalised estimating equation; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least squares; MID, minimally important difference; NRI, non-responder imputation; PASDAS, Psoriasis Arthritic Disease Activity Score; PASI75/90/100, 75/90/100% improvement in Psoriasis Area and Severity Index; PBO, placebo; PsA, psoriatic arthritis; Q2W, every 2 weeks.