Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo- and active comparatorecontrolled phase 3 AMAGINE-2 trial Luis Puig, MD,a Mark Lebwohl, MD,b Herve Bachelez, MD,c,d Jeffrey Sobell, MD,e and Abby A. Jacobson, PA-Cf Barcelona, Spain; New York, New York; Paris, France; Chestnut Hill, MA; and Bridgewater, NJ Background: Randomized controlled trials have shown the efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis. Objective: To evaluate the efficacy and safety of brodalumab through 120 weeks of treatment in the AMAGINE-2 trial. Methods: Patients received ustekinumab through week 52 followed by brodalumab 210 mg every 2 weeks, continuous brodalumab 210 mg every 2 weeks, or any dose of brodalumab. Efficacy data were reported through 120 weeks by using observed data, last observation carried forward, and nonresponder imputation analyses. Results: Of patients who received brodalumab 210 mg every 2 weeks, 84.4%, 75.6%, and 61.1% achieved 75%, 90%, and 100% improvement from baseline in Psoriasis Area and Severity Index at 120 weeks (observed data analysis), respectively. Patients who received brodalumab 210 mg every 2 weeks after receiving ustekinumab through 52 weeks achieved a similar skin clearance response as patients who received continuous brodalumab 210 mg every 2 weeks. Safety through 120 weeks was comparable to that of the blinded study periods. From the Hospital de la Santa Creu i Sant Pau, Universitat Boehringer-Ingelheim, Celgene, Dermavant, Janssen, Leo, Lilly, Aut onoma de Barcelona, Barcelonaa; Icahn School of Medicine Mylan, Novartis, Pfizer, Sun, Takeda, and UCB and has received at Mount Sinai, New Yorkb; Sorbonne Paris Cite Universite Paris grant support from Pfizer. Dr Sobell has served as an Diderotc; AP-HP H^ opital Saint-Louis, Parisd; SkinCare Physicians, investigator, consultant, and/or speaker for Amgen, AbbVie, Chestnut Hille; and Ortho Dermatologics, Bridgewater.f Janssen Biotech, Celgene, Merck, Sun, Lilly, Novartis, UCB, Funding sources: Supported by Ortho Dermatologics. The Regeneron, and Sanofi. Ms Jacobson is an employee of Ortho AMAGINE-2 study was supported by Amgen. Dermatologics and holds stocks and/or stock options in Bausch Disclosure: Dr Puig has received consulting fees, speaking fees, Health. and/or honoraria from AbbVie, Almirall, Amgen, Baxalta, Accepted for publication May 31, 2019. Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, Leo, Reprints not available from the authors. Eli Lilly and Company, Merck-Serono, MSD, Novartis, Pfizer, Correspondence to: Luis Puig, MD, Hospital de la Santa Creu i Sant Regeneron, Roche, and Sandoz and has received institutional Pau, Universitat Autonoma de Barcelona, Dept of Dermatology, research funding related to the treatment of psoriasis from Mas Casanovas 90, Block A, 5th Floor, Module 3, 08041 AbbVie, Amgen, Janssen, Eli Lilly and Company, Novartis, and Barcelona, Spain. E-mail: lpuig@santpau.cat. Pfizer. Dr Lebwohl is an employee of Mount Sinai and receives Published online June 5, 2019. research funds from Abbvie, Boehringer Ingelheim, Celgene, Eli 0190-9622 Lilly, Incyte, Janssen, Johnson & Johnson, Leo, MedImmune/As- Ó 2019 by the American Academy of Dermatology, Inc. Published traZeneca, Novartis, Pfizer, SciDerm, Valeant, and Vidac and is by Elsevier Inc. This is an open access article under the CC also a consultant for Allergan, Aqua, Boehringer-Ingelheim, Leo, BY-NC-ND license (http://creativecommons.org/licenses/by-nc- Menlo, and Promius. Dr Bachelez has served as a consultant, nd/4.0/). speaker, steering committee member, investigator, or advisory https://doi.org/10.1016/j.jaad.2019.05.095 board member for AbbVie, Almirall, Amgen, Baxalta, 352 J AM ACAD DERMATOL Puig et al 353 VOLUME 82, NUMBER 2 Limitations: A large number of discontinuations toward the end of the study (31% in the final 6 months) were due to early termination and led to differences between observed data and nonresponder imputation results. Conclusions: Brodalumab is well tolerated and showed robust efficacy for more than 2 years. ( J Am Acad Dermatol 2020;82:352-9.) Key words: AMAGINE-2; brodalumab; efficacy; long-term; psoriasis; safety. Despite recent improve- after ustekinumab, patients ments in systemic treatment CAPSULE SUMMARY who received only brodalu- for psoriasis, there is an un- mab 210 mg every 2 weeks, met need for biologic thera- and all patients who received d Sustained skin clearance is an unmet pies that do not lose efficacy any dose of brodalumab. need in patients with psoriasis. over time. However, the mechanisms underlying loss d Brodalumab showed sustained skin METHODS of efficacy are multifactorial clearance through 120 weeks, with Study design and patients and not completely under- 61.1% of patients achieving 100% AMAGINE-2 (ClinicalTrials. stood.1 Studies reporting improvement from baseline in Psoriasis gov identifier NCT01708603) skin clearance efficacy of bi- Area and Severity Index (observed data was a randomized, double- ologics with 2 to 3 years of analysis) and no new safety signals, blind, placebo- and active follow-up have shown main- suggesting that brodalumab is an comparatorecontrolled phase tenance of Psoriasis Area and efficacious long-term treatment. 3 trial that has been previously Severity Index (PASI) of 75% described.8 Patients were improvement from baseline 18 to 75 years of age and (PASI 75) in 83.0% to 93.4% of participants.2-4 With had moderate to severe plaque psoriasis diagnosed regard to long-term complete skin clearance, open- at least 6 months before the first dose of brodalumab label extension studies have shown 100% improve- with involved body surface area 10% or greater, PASI ment in PASI over baseline (PASI 100) (observed data score of 12 or greater, and static physician’s global analysis) in 43.8%, 56.3%, and 42.6% of patients after assessment (sPGA) score of 3 or greater at screening 160 weeks of ustekinumab, 108 weeks of ixekizu- and at baseline. Patients were randomly assigned to mab, and 152 weeks of secukinumab, respectively.2-4 receive brodalumab (140 or 210 mg every 2 weeks), Drugs associated with increased rates of complete ustekinumab, or placebo during the 12-week skin clearance over long periods of time may have a induction phase, followed by a maintenance phase long-term positive effect on health-related quality of through week 52 (Supplemental Fig 1; available at life in patients with psoriasis.5 http://dx.doi.org/10.17632/6jghtvc333.1). During the Brodalumab is a fully human antieinterleukin (IL) maintenance phase, patients who received brodalu- 17 receptor A monoclonal antibody approved for the mab were randomly reassigned to receive brodalumab treatment of moderate to severe psoriasis in patients 140 mg every 2 weeks, every 4 weeks, or every 8 weeks who have inadequate response to other systemic or 210 mg every 2 weeks; patients receiving ustekinu- therapies.6 The efficacy and safety of brodalumab mab continued to receive ustekinumab; and patients have been shown in 1 phase 2 and 3 phase 3 clinical receiving placebo were switched to brodalumab trials (AMAGINE-1/-2/-3) in which brodalumab 210 mg every 2 weeks. Patients receiving brodalumab showed superior skin clearance efficacy at week 12 who experienced inadequate response between compared with placebo (AMAGINE-1/-2/-3) and weeks 16 and 52 and patients receiving ustekinumab ustekinumab (AMAGINE-2/-3).7,8 At week 12, PASI experiencing inadequate response at week 16 were 75 response rates were 83.3%, 86%, and 85% for switched to brodalumab 210 mg every 2 weeks (rescue AMAGINE-1, -2, and -3, respectively, and PASI 100 phase), as described previously.8 At week 52, patients response rates were 41.9%, 44%, and 37%, receiving brodalumab continued to receive brodalu- respectively.7,8 mab at their maintenance or rescue phase dosage, and Here, we compare efficacy and safety data from patients who were originally assigned to received the open-label extension of AMAGINE-2 in patients ustekinumab were switched to brodalumab 210 mg who received brodalumab 210 mg every 2 weeks every 2 weeks. Data are shown for patients who 354 Puig et al J AM ACAD DERMATOL FEBRUARY 2020 or interval of brodalumab (140 mg every 2 weeks, Abbreviations used: every 4 weeks, or every 8 weeks or 210 mg every AE: adverse event 2 weeks) in the long-term extension, after receiving IL: interleukin LOCF: last observation carried forward either any dose or interval of brodalumab (n = 1790) NRI: nonresponder imputation or ustekinumab (n = 274) in the maintenance phase. PASI: Psoriasis Area and Severity Index Data for patients who received continuous brodalu- PASI 75: 75% improvement in Psoriasis Area and Severity Index mab 210 mg every 2 weeks during the induction, PASI 90: 90% improvement in Psoriasis Area and maintenance, and long-term extension phases Severity Index (n = 168) were also analyzed by using observed PASI 100: 100% improvement in Psoriasis Area and Severity Index data and imputed data (either using the last obser- SIB: suicidal ideation and behavior vation carried forward [LOCF] method or nonre- sPGA: static physician’s global assessment sponder imputation [NRI] method). The observed TEAE: treatment-emergent adverse event data analysis included data for patients with a valid measurement at the specified time point, with no steps taken to account for missing data. The LOCF received brodalumab 210 mg every 2 weeks after analysis replaced missing data with the most recently receiving ustekinumab through week 52, patients who observed value. The NRI analysis assumed nonre- received continuous brodalumab 210 mg every sponse for all missing data.10 2 weeks, and all patients who received any dose of brodalumab. RESULTS All patients provided written informed consent Patient characteristics before the initiation of study procedures. AMAGINE- Baseline demographics and disease characteris- 2 study protocols were consistent with the 2008 tics are shown in Table I. Patients who were initially Declaration of Helsinki and the International randomly assigned to receive ustekinumab had Conference on Harmonisation of Technical similar demographics and disease characteristics as Requirements for Registration of Pharmaceuticals patients who received continuous brodalumab for Human Use for Good Clinical Practice and were 210 mg every 2 weeks. approved by individual institutional review boards at Discontinuations in patients who received contin- each participating study center. uous brodalumab 210 mg every 2 weeks are shown in Supplemental Table I (available at http://dx.doi. Clinical assessments org/10.17632/6jghtvc333.1). A notable increase in Skin clearance efficacy was monitored through discontinuations after week 85 was observed, with week 120 by the sPGA and PASI. The percentages of most of these discontinuations attributed to the early patients achieving PASI 75, 90% improvement in PASI termination of the study by the sponsor. The median over baseline (PASI 90), or PASI 100 were deter- duration of exposure in patients who received any mined. Efficacy end points during the long-term dose of brodalumab through the end of study was extension phase focus on week 120 because the 24.0 (range, 0.3-35.0) months. study was ended prematurely by the sponsor, and most patients who were continuing to receive Efficacy treatment had undergone efficacy assessments at On the basis of the observed data analysis, skin that study visit. Safety was assessed by monitoring clearance efficacy was maintained from week 52 treatment-emergent adverse events (TEAEs), and through week 120 in patients who received contin- serious adverse events (AEs) and were summarized uous brodalumab 210 mg every 2 weeks (Fig 1). by treatment group. TEAEs are shown as exposure- Starting at week 52, patients who switched to adjusted event rates per 100 patient-years from the brodalumab 210 mg every 2 weeks after receiving first dose of brodalumab through the end of the ustekinumab experienced increased sPGA score of study. Rates of depression and suicidal ideation and 0 or 1 (sPGA 0/1), PASI 90, and PASI 100 response behavior (SIB) were calculated as follow-up obser- rates that were maintained through week 120 (Fig 1, vation timeeadjusted rates per 100 patient-years A). Among patients who switched from ustekinu- from the first dose of brodalumab through the end mab to brodalumab, PASI 100 response rates were of the study, as described previously.9 43.4% at week 52, had increased to 60.7% by week 56, and remained stable through week 120. Patients Statistical analysis who received continuous brodalumab 210 mg every Long-term efficacy was analyzed by using 2 weeks achieved a PASI 100 response rate of 64.8% observed data for patients who received any dose at week 52, which was maintained through week J AM ACAD DERMATOL Puig et al 355 VOLUME 82, NUMBER 2 120 (Fig 1, B). Skin clearance efficacy was also rates based on observed data analysis, respectively. maintained from week 52 through week 120 among Before week 52, 15 patients in the group receiving patients who received any dose of brodalumab, continuous brodalumab 210 mg every 2 weeks with a small numeric decrease in efficacy from discontinued treatment. weeks 96 to 120 (Fig 1, C ). Patients who received continuous brodalumab For patients who received continuous brodalu- 210 mg every 2 weeks had more rapid onset of skin mab 210 mg every 2 weeks, LOCF analysis showed clearance response than patients who received skin clearance response rates similar to those with ustekinumab or any dose of brodalumab in the observed data analysis (Supplemental Fig 2; avail- maintenance phase (Supplemental Fig 3; available able at http://dx.doi.org/10.17632/6jghtvc333.1). at http://dx.doi.org/10.17632/6jghtvc333.1). As early However, skin clearance estimates in the NRI anal- as week 2, patients who received continuous broda- ysis were consistently less than corresponding esti- lumab 210 mg every 2 weeks showed a mean mates in the observed data analysis after week 52. decrease in baseline PASI score of 57.1%, compared On the basis of the observed data, LOCF, and NRI with a mean decrease of 29.4% and 41.1% at week 2 analyses, PASI 75 was achieved in 84.4% (76/90), in patients who received ustekinumab or any dose of 81.0% (136/168), and 45.2% (76/168) of patients who brodalumab in the maintenance phase, respectively. received continuous brodalumab at week 120, Mean percent decrease in baseline PASI score was respectively, and PASI 100 was achieved in 61.1% maintained at approximately 90% with continuous (55/90), 50.0% (84/168), and 32.7% (55/168) of brodalumab 210 every 2 weeks from week 18 patients, respectively. sPGA 0/1, PASI 75, PASI 90, onward. and PASI 100 response rates based on NRI analysis at week 52 were 11.8%, 12.7%, 11.9%, and 8.8% less Safety than rates based on observed data analysis, respec- The overall exposure-adjusted event rate of tively. At week 120, sPGA 0/1, PASI 75, PASI 90, and TEAEs among all patients who received any dose PASI 100 response rates based on NRI analysis were of brodalumab in the long-term extension was 306.9 37.6%, 39.2%, 35.1%, and 28.4% less than response per 100 patient-years from the first dose of Table I. Patient demographics and baseline disease characteristics* Continuous All patients who Brodalumab 210 mg brodalumab 210 mg received any dose every 2 weeks after every 2 weeks of brodalumab Demographics and characteristics ustekinumab (n = 274) (n = 168) (n = 1790) Age in years, mean 6 SD 45.7 6 12.9 43.7 6 13.5 44.6 6 12.8 Sex, n (%) Male 189 (69.0) 116 (69.0) 1233 (68.9) Female 85 (31.0) 52 (31.0) 557 (31.1) Race, n (%) American Indian or Alaska Native 1 (0.4) 1 (0.6) 7 (0.4) Asian 12 (4.4) 4 (2.4) 68 (3.8) Black (or African American) 4 (1.5) 4 (2.4) 50 (2.8) Multiple 3 (1.1) 1 (0.6) 10 (0.6) Native Hawaiian or other Pacific Islander 0 (0.0) 1 (0.6) 9 (0.5) White 248 (90.5) 153 (91.1) 1615 (90.2) Other 6 (2.2) 4 (2.4) 31 (1.7) Psoriatic arthritis, n (%) No 228 (83.2) 130 (77.4) 1459 (81.5) Yes 46 (16.8) 38 (22.6) 331 (18.5) Duration of psoriasis in years, mean 6 SD 19.3 6 12.8 16.9 6 11.6 18.6 6 12.2 PASI, mean 6 SD 19.9 6 8.2 20.2 6 8.0 20.3 6 8.2 % BSA, mean 6 SD 27.0 6 19.6 25.4 6 15.3 26.8 6 17.25 sPGA, n (%) 3 136 (49.6) 92 (54.8) 971 (54.2) 4 124 (45.3) 65 (38.7) 707 (39.5) 5 14 (5.1) 11 (6.5) 112 (6.3) BSA, Body surface area; PASI, Psoriasis Area and Severity Index; SD, standard deviation; sPGA, static physician’s global assessment. *Treatment groups are as treated after first dose of active brodalumab. 356 Puig et al J AM ACAD DERMATOL FEBRUARY 2020 Fig 1. Rates of sPGA 0/1, PASI 75, PASI 90, and PASI 100 response through week 120 among (A) patients who received brodalumab 210 mg every 2 weeks after ustekinumab at week 52, J AM ACAD DERMATOL Puig et al 357 VOLUME 82, NUMBER 2 Table II. Exposure-adjusted event rates of adverse events from the first dose of brodalumab through the end of the study* Brodalumab 210 mg Continuous brodalumab All patients who received every 2 weeks after 210 mg every 2 weeks any dose of brodalumab Exposure and AEs ustekinumab (n = 274) (n = 168) (n = 1790) Total PY of exposure 343.1 339.1 3228.5 Number of AEs (exposure-adjusted event rate per 100 PY)y All TEAEs 908 (264.7) 1084 (319.7) 9909 (306.9) Grade $2 558 (162.6) 659 (194.3) 5601 (173.5) Grade $3 29 (8.5) 43 (12.7) 395 (12.2) Serious 22 (6.4) 30 (8.8) 247 (7.7) Leading to discontinuation of brodalumab 17 (5.0) 15 (4.4) 103 (3.2) Leading to discontinuation from study 5 (1.5) 9 (2.7) 61 (1.9) Fatal 0 (0) 0 (0) 1 (0)z AE, Adverse event; TEAE, treatment-emergent adverse event; PY, patient-years. *Multiple occurrences of the same event for a patient are counted as multiple events. y Exposure-adjusted event rate per 100 PY calculated as n/total PY of exposure through end of study 3 100. z One death occurred during the exposure period. brodalumab through the end of the study (Table II). (0.0, 0.1, 0.1, and 0.2 per 100 patient-years, Corresponding rates in patients who received bro- respectively), with these AEs occurring 1, 2, 3, and dalumab 210 mg every 2 weeks after receiving 8 times throughout the study, respectively. ustekinumab and continuous brodalumab 210 mg Rates of depression and SIB were calculated every 2 weeks were 264.7 and 319.7 events per 100 separately as follow-up observation timeeadjusted patient-years, respectively. Similar rates of serious rates. The rates of depression and suicidal ideation AEs and AEs leading to discontinuation were and behavior AEs were 3.0 and 0.58 per 100 patient- observed across all treatment groups. Among all years, respectively, in patients who received any patients who received any dose of brodalumab in the dose of brodalumab. Rates of self-injury, attempted long-term extension, the exposure-adjusted rate of suicide, and completed suicides were 0.03, 0.15, and all TEAEs was highest in the first year of treatment 0.06, respectively. and decreased in subsequent years (Supplemental Supplemental data are available at http://dx.doi. Table II; available at http://dx.doi.org/10.17632/ org/10.17632/6jghtvc333.1. 6jghtvc333.1). Among the most frequent TEAEs in all brodalumab treatment groups throughout the DISCUSSION duration of the study were arthralgia, headache, Skin clearance, as determined by sPGA 0/1, PASI diarrhea, oropharyngeal pain, and Candida species 75, PASI 90, and PASI 100 response rates, was infections. The exposure-adjusted event rate of increased after week 52 and maintained through arthralgia of at least grade 2 and at least grade 3 week 120 in patients who received brodalumab throughout the duration of the study was 4.0 and 0.2 210 mg every 2 weeks after receiving ustekinumab per 100 patient-years, respectively. Consistent with and was maintained from weeks 52 to 120 in patients the yearly rates of all TEAEs, the rates for the most who received continuous brodalumab 210 mg every frequent TEAEs and other TEAEs of interest generally 2 weeks and in all patients who received any dose of declined over time. Furthermore, exposure-adjusted brodalumab, with a slight decrease from week 96 to event rates of other psoriasis phenotypes, week 120. Many patients who received ustekinumab including erythrodermic, guttate, nail, and pustular until week 52 achieved better skin clearance psoriasis, were relatively low throughout the study response rates after switching to brodalumab 210 = (B) continuous brodalumab 210 mg every 2 weeks, or (C) any dose of brodalumab. All analyses are as observed. Error bars show the 95% confidence intervals. Arrow in panel (A) indicates rates after the switch to brodalumab 210 mg every 2 weeks. n1, Number of patients who had a valid measurement value at the specified week; PASI 75, 75% improvement in Psoriasis Area and Severity Index; PASI 90, 90% improvement in Psoriasis Area and Severity Index; PASI 100, 100% improvement Psoriasis Area and Severity Index; Q2W, every 2 weeks; sPGA 0/1, static physician’s global assessment score of 0 or 1. 358 Puig et al J AM ACAD DERMATOL FEBRUARY 2020 every 2 weeks during the long-term extension. received brodalumab during the open-label exten- Notably, 57.5% of these patients achieved PASI 100 sion achieved PASI 75 at weeks 52 and 120, respec- after 120 weeks, suggesting that brodalumab may be tively. The maintenance of efficacy observed with efficacious in patients who received ustekinumab. brodalumab may be related to the lack of neutral- Patients who received continuous brodalumab izing antidrug antibodies detected in any samples in 210 mg every 2 weeks experienced a greater percent AMAGINE-2 (data not shown). change from baseline in PASI score at week 2 Point estimates for skin clearance efficacy based on compared with patients in other treatment groups. NRI analysis were generally less than the correspond- Although cross-trial comparisons are complicated ing estimates in the observed data analysis from by variability in many parameters, long-term rates of weeks 52 to 120, with differences ranging from 8.8% skin clearance efficacy (as determined by PASI 75 to 12.7% at week 52 and 28.4% to 39.2% at week 120. response) in this open-label extension were greater Prior studies evaluating secukinumab have shown than the rates observed at similar time points in trials differences between PASI 90 response rates at week of ustekinumab and similar to rates observed in long- 52 based on NRI estimates and observed data analyses term trials of secukinumab, an antieIL-17A to be less than 10%.10 Similar observations were seen biologic.2,4,11 using matching statistical analysis in studies evaluating ixekizumab, where PASI 75, PASI methodology. Rates of complete skin clearance 90, and PASI 100 response rates based on modified (determined by PASI 100 response and using match- NRI analysis were 16.7%, 20.7 %, and 18.8% less than ing statistical analysis methodology) were greater rates based on observed data analysis at week 156.12 than corresponding estimates at similar time points Discontinuation may explain the difference between in trials of ustekinumab and secukinumab and NRI and observed data analyses in our study.10 similar to rates observed in long-term trials of Decreases in NRI point estimates beginning at week ixekizumab.2,4,12 Studies have shown that patients 96 may have resulted from the increased withdrawal who achieve complete skin clearance have rate beginning at approximately week 96 with the improved symptom- and quality-of-lifeerelated out- public announcement of study termination. The me- comes than patients who do not.5 The increased dian duration of brodalumab exposure through the likelihood of achieving complete skin clearance end of the study was 24 months, but it is possible that associated with brodalumab may allow improve- external factors rather than treatment-related factors ment of patient quality of life relative to other influenced NRI analyses, resulting in decreased skin biologics associated with a lesser rate of achieving clearance efficacy rates relative to observed data complete skin clearance. The observed numerically analyses after week 52. greater efficacy rates with brodalumab versus rates The safety profile of brodalumab during long- with other biologics may be due to the inhibition of term follow-up was similar to that observed during IL-17 receptor instead of upstream components of the blinded study periods, and no new safety signals the IL-17 pathway. were observed during the long-term extension. Rates Efficacy and safety evaluations of monoclonal of overall TEAEs decreased over time relative to antibodies that target IL-23 show PASI 100 response preceding years. The most common AEs were also rates of 32% at 28 weeks (observed data analysis) and consistent with those observed in other brodalumab 50% at 100 weeks (observed data analysis) in patients psoriasis clinical trials.15,16 Relatively low rates of AEs who received tildrakizumab and guselkumab, of special interest, such as Candida infection (3.9 per respectively, compared with 58% and 63% at 28 100 patient-years), were observed with long-term and 108 weeks, respectively (all observed data brodalumab treatment, similar to rates with secuki- analysis) in patients who received continuous bro- numab.4 The overall rate of AEs associated with dalumab.13,14 Real-world studies are needed to fully brodalumab was similar to that observed during characterize the long-term efficacy and safety of long-term ustekinumab studies, where ustekinumab these treatments. was associated with 305.9 events per 100 patient- A study evaluating loss of efficacy of biologic years after 3 years.17 Common AEs associated with agents including etanercept, adalimumab, ustekinu- brodalumab, including headache and arthralgia, mab, and infliximab long-term (0.8-3.9 years) has were similar to those observed in long-term studies shown that 20%-32% of patients lose PASI 75 evaluating ustekinumab and secukinumab.4,17 response throughout the duration of treatment.1 In conclusion, long-term data show sustained This observed decrease in efficacy over time is efficacy and consistent safety profile with brodalu- usually associated with formation of antidrug anti- mab for more than 2 years. Most patients who bodies that can inactivate therapeutic effects.1 Our received brodalumab 210 mg every 2 weeks after findings show that 91.2% and 88.9% of patients who ustekinumab treatment achieved complete skin J AM ACAD DERMATOL Puig et al 359 VOLUME 82, NUMBER 2 clearance after 120 weeks, suggesting that brodalu- 8. Lebwohl M, Strober B, Menter A, et al. Phase 3 studies mab may be well suited for long-term treatment of comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373(14):1318-1328. moderate to severe psoriasis in patients who 9. Lebwohl MG, Papp KA, Marangell LB, et al. Psychiatric received prior systemic therapy. Although cross- adverse events during treatment with brodalumab: analysis trial comparisons are complicated by the variability of psoriasis clinical trials. J Am Acad Dermatol. 2018;78(1):81- of many parameters, compared with other biologics 89.e85. used to treat psoriasis, brodalumab was associated 10. 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