Takaisin

Effectiveness of abrocitinib compared to placebo in treatment of atopic dermatitis

Näytönastekatsaukset
Raija Sipilä and Jorma Komulainen
30.5.2023

Level of evidence: A

Abrocitinib in dose of 100 or 200 mg once daily alone or in combination with topical treatment increases the proportion of patients (age at least 12 years) with moderate-to-severe atopic dermatitis achieving EASI-75 response at week 12, when compared to placebo (100 mg: 40-58.7%, 200 mg: 61.0-70.3%, and placebo 10.4-27.1%).

In addition, abrocitinib compared to placebo increases the proportion of patients with improvement in peak score on numerical rating scale (NRS) for pruritus and appears to increase the proportion of patients achieving EASI90, and appears to improve the quality of life. The evidence is based on 4 RCTs, applicability of the evidence is high.

Table 1. Description of the included studies
Reference Study type Population Intervention and comparison Outcomes Risk of bias
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis; AE=adverse event; IGA=Investigators Global Assessment; EASI=Eczema Area and Sensitivity Index; PP-NRS=Peak Pruritus-Numerical Rating Scale; SCORAD=SCORing Atopic Dermatitis, DLQI=Dermatology-specific quality of life; POEM=Patient-Oriented Eczema Measure; PSAAD=Symptoms Assessment for Atopic Dermatitis.
* Results for dupilumab group (n=243) not shown in the evidence summary.
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 SR/MA including 4 RCTs RCTs reporting outcomes of interest, patients at least 12 years of age diagnosed with
moderate-to-severe atopic eczema for at least 1 year before the screening
visit and responding inadequately to the topical medications.
N of patients 1509.
oral abrocitinib 100 or 200 mg
once daily with or without topical agents and placebo
Primary:
proportion of patients achieving IGA response at 12 weeks.
Secondary: Proportion of patients achieving EASI-75 response, PP-NRS response, developing treatment-emergent
AEs
Low
«Silverberg JI, Simpson EL, Thyssen JP ym. Efficacy...»2 RCT Patients ≥ 12 years of age (and body weight over 40 kg) with moderate to severe atopic eczema (EASI ≥ 16 and an IGA score of ≥ 3), an inadequate response to topical treatments or topical calcineurin inhibitors,
a history of topical atopic eczema treatments being considered medically
inadvisable, or a history of receiving systemic therapies
for atopic eczema.
N=554
oral abrocitinib once daily 100 or 200 mg or placebo Primary: the proportion
of patients achieving IGA response 0/1
and EASI-75 response.
Secondary: PP-NRS, EASI-50, EASI-90, SCORAD, adverse vents
Moderate
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3 RCT Patients >12 years of age (and body weight over 40 kg) with moderate to severe atopic eczema (EASI ≥ 16 and an IGA score of ≥ 3), an inadequate response to topical treatments or topical calcineurin inhibitors,
a history of topical atopic eczema treatments being considered medically
inadvisable, or a history of receiving systemic therapies
for atopic eczema.
N=387
oral abrocitinib once daily 100 or 200 mg or placebo Primary: the proportion
of patients achieving IGA response 0/1
and EASI-75 response.
Secondary: PP-NRS, EASI-50, EASI-90, SCORAD, POEM, DLQI, adverse events
Low
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4 RCT Patients ≥18 years of age with moderate to severe atopic eczema (EASI ≥ 16 and an IGA score of ≥ 3), an inadequate response to topical treatments or topical calcineurin inhibitors,
a history of topical atopic eczema treatments being considered medically
inadvisable, or a history of receiving systemic therapies
for atopic eczema.
N= 838
oral abrocitinib once daily 100 or 200 mg, 300 mg of dupilumab * subcutaneously
every other week (after a loading dose of
600 mg), or placebo. Topical treatment was allowed. Primary: the proportion
of patients achieving IGA response 0/1
and EASI-75 response.
Secondary: PP-NRS, EASI50, EASI-90, SCORAD, POEM, DLQI, adverse events
Low
Table 2. Additional comments for included studies
Reference Comments
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 Literature search was performed from PubMed, Cochrane, and the International Clinical Trials Registry Platform (ICTRP) until April 30, 2021. From included studies one was phase II study. The risk of bias of included studies was low.
Two studies had included participants 12 years or older
and two studies had involved participants aged 18 years or
above.
«Silverberg JI, Simpson EL, Thyssen JP ym. Efficacy...»2 A multi-center study in Australia, Bulgaria, Canada, China, Czechia, Germany, Hungary, Japan, South Korea, Latvia, Poland, United Kingdom, and the United States. Patients who had previously
used systemic JAK inhibitors or dupilumab
or had a medical history of conditions
associated with thrombocytopenia, coagulopathy,
or platelet dysfunction were ineligible. Approximately 10 % of patients were under 18 years of age.
Patients were permitted to use oral antihistamines
and topical nonmedicated emollients. Randomization was stratified by baseline disease severity (IGA score of 3 or 4) and age group (<18 or ≥18 years). A third (33.3%) of patients in the placebo group discontinued the treatment whereas the respective numbers for abrocitinib groups were 13.3% and 9%.
The study was sponsored by pharma.
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3 A multi-center study in Australia, Canada, Europe, and the USA. Patients were permitted to use oral anti histamines and topical nonmedicated emollients during the study. Patients who had previously
used systemic JAK inhibitors or dupilumab
or had a medical history of conditions
associated with thrombocytopenia, coagulopathy,
or platelet dysfunction were ineligible. Use of topical therapies for atopic dermatitis (corticosteroids, calcineurin inhibitors, tars, antibiotic creams, and topical antihistamines) and rescue medication was not permitted. Randomisation was stratified by baseline disease severity (Investigator Global Assessment score 3 or 4) and age group (<18 years or ≥18 years).
The study was sponsored by pharma.
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4 A multi-center study in 18 countries (Australia and countries across North and South America, Europe, and Asia). Patients who had previously
used systemic JAK inhibitors or dupilumab or had a medical history of conditions
associated with thrombocytopenia, coagulopathy, or platelet dysfunction were ineligible. Emollients were used twice daily throughout the trial. Topical therapies that were allowed during the trial included low- or medium potency topical glucocorticoids, topical calcineurin inhibitors, and topical phosphodiesterase 4 inhibitors. Patients were allowed to use more than one topical agent. Rescue therapy with systemic medications or topical treatments was not permitted.
The study was sponsored by pharma.

Results

Table 3. Outcome 1: EASI-75 (number and proportion of patients achieving EASI-75)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C ARR or RR* (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; RR=risk ratio
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 Abrocitinib 100 mg
4 RCTs (600/334)
12 291 (48.5) 60 (18) RR 2.74 (1.99-3.79)
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 Abrocitinib 200 mg
4 RCTs (574/334)
12 375 (65.3) 60 (18) RR 4.04 (2.55-6.42)
«Silverberg JI, Simpson EL, Thyssen JP ym. Efficacy...»2 Abrocitinib 100 mg, no concomitant topical treatment allowed
(158 /78)
12 69 (44.5) 8 (10.4) 33.9 (23.3-44.4)
Abrocitinib 200 mg, no concomitant topical treatment allowed
(155 /78)
12 94 (61.0) 8 (10.4) 50.5 (40.0-60.9)
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3 Abrocitinib 100 mg, no concomitant topical treatment allowed
(156 /77)
12 62 (40) 9 (12) 27.9 (17.4-38.3)
Abrocitinib 200 mg, no concomitant topical treatment allowed
(154 /77)
12 96 (63) 9 (12) 51 (40.5-61.5)
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4 Abrocitinib 100 mg, concomitant topical treatment allowed
(238 /131)
12 138 (58.7) 35 (27.1) 31.9 (22.2-41.6)
Abrocitinib 200 mg, concomitant topical treatment allowed
(226 /131)
12 154 (70.3) 35 (27.1) 43.2 (33.7-52.7)
Level of evidence: high.
Table 4. Outcome 2: EASI-90 (number and proportion of patients achieving EASI-90)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C ARR (95% CI)
I=intervention; C=comparison; CI=confidence interval; NA=not available; ARR=Absolute risk reduction
«Silverberg JI, Simpson EL, Thyssen JP ym. Efficacy...»2 Abrocitinib 100 mg, no concomitant TCS allowed
(158 /78)
12 37 (23.9) 3 (3.9) 20.1 (11.9-28.3)
Abrocitinib 200 mg, no concomitant TCS allowed
(155 /78)
12 58 (37.7) 3 (3.9) 33.5 (24.6-42.5)
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3 Abrocitinib 100 mg, no concomitant TCS allowed
(156 /77)
12 29 (19) 4 (5) 13.3 (5.4-21.2)
Abrocitinib 200 mg, no concomitant TCS allowed
(154 /77)
12 59 (39) 4 (5) 33.4 (24.3-42.5)
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4 Abrocitinib 100 mg, concomitant topical treatment allowed (238 /131) 12 86 (36.6) 13 (10.1) NA
Abrocitinib 200 mg, concomitant topical treatment allowed (226 /131) 12 101 (46.1) 13 (10.1) NA
Level of evidence: Moderate
The quality of evidence is downgraded due to imprecision (one study for concomitant topical treatment and confidence intervals not reported).
Table 5. Outcome 3: IGA (Investigator's Global Assessment (IGA) score achieved 0/1)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C ARR or RR (95% CI)
I=intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; RR=risk ratio  
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 Abrocitinib 100 mg
4 RCTs (600/334)
12  183 (30.5) 34 (10.2) RR 2.94 (2.10-4.13)
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 Abrocitinib 200 mg
4 RCTs (575/334)
12 253 (44) 34 (10.2) RR 4.18 (3.00-5.81)
«Silverberg JI, Simpson EL, Thyssen JP ym. Efficacy...»2 Abrocitinib 100 mg, no concomitant TCS allowed
(158 /78)
12 44 (28.4) 7 (9.1) 19.3 (9.6-29.0)
Abrocitinib 200 mg, no concomitant TCS allowed
(155 /78)
12 59 (38.1) 7 (9.1) 28.7 (18.6-38.8)
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3 Abrocitinib 100 mg, no concomitant TCS allowed
(156 /77)
12 37 (24) 6 (8) 15.8 (6.8-24.8)
Abrocitinib 200 mg, no concomitant TCS allowed
(154 /77)
12 67 (44) 6 (8) 36.0 (26.2-45.7)
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4 Abrocitinib 100 mg, concomitant topical treatment allowed (238 /131) 12 86 (36.6) 18 (14.0) 23.1 (14.7-31.4)
Abrocitinib 200 mg, concomitant topical treatment allowed (226 /131) 12 106 (48.4) 18 (14.0) 34.8 (26.1-43.5)
Level of evidence: high.
Table 6. Outcome 4: Pruritus (Improvement in weekly average of worst daily pruritus NRS ≥ 4 points from baseline)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C ARR or RR (95% CI)
I= intervention; C=comparison; CI=confidence interval; ARR=Absolute risk reduction; RR=risk ratio; * post hoc analysis
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 Abrocitinib 100 mg
4 RCTs (578/323)
12 256 (40.7) 68 (21.1) RR 2.94 (2.10-4.13)
«Meher BR, Mohanty RR, Padhy BM. Efficacy and safet...»1 Abrocitinib 200 mg
4 RCTs (565/323)
12 334 (59.1) 68 (21.1) RR 4.18 (3.00-5.81)
«Silverberg JI, Simpson EL, Thyssen JP ym. Efficacy...»2 Abrocitinib 100 mg, no concomitant TCS allowed
(158 /78)
12 71 (45.2) 9 (11.5) 33.7 (22.8-44.7)
Abrocitinib 200 mg, no concomitant TCS allowed
(158 /78)
12 85 (55.3) 9 (11.5) 43.9 (32.9-55.0)
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3 Abrocitinib 100 mg, no concomitant TCS allowed
(156 /77)
12 55 (38) 11 (15) 22.5 (10.3-34.8)
Abrocitinib 200 mg, no concomitant TCS allowed
(154 /77)
12 84 (57) 11 (15) 41.7 (29.6-53.9)
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4 Abrocitinib 100 mg, concomitant topical treatment allowed (238 /131)
12* 105 (47.5) 35 (28.9) 18.5 (8.0-28.9)
Abrocitinib 200 mg, concomitant topical treatment allowed (226 /131) 12* 137 (63.1) 35 (28.9) 33.7 (23.4-44.1)
Level of evidence: high.
Table 7. Outcome 4: Dermatology Life Quality Index (DLQI) (*The mean change in DLQI or *patients with ≥4-point decrease in DLQI total score— no. (%))
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Mean change from baseline (95% CI) or Absolute number of events (%) I Mean change from baseline (95% CI) or Absolute number of events (%) C Relative effect (95% CI)
I=intervention; C=comparison; CI=confidence interval; * assessed for patients over 18 years of age
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3* Abrocitinib 100 mg, no concomitant TCS allowed
(121 /60)
12 -7.0 (-8.1 – -5.8) -4.2 (-5.9 – -2.5) -2.8 (-4.8 – -0.8)
Abrocitinib 200 mg, no concomitant TCS allowed
(119//60)
12 -9.1 (-10.3 – -8.0) -4.2 (-5.9 – -2.5) -4.9 (-6.9 – -2.9)
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4** Abrocitinib 100 mg, concomitant topical treatment allowed (238 /131)
12 171 (74.7) 70 (56.5) NA
Patients with ≥4-point decrease in DLQI total score—
no. (%)
Abrocitinib 200 mg, concomitant topical treatment allowed (226 /131) 12 190 (86.4) 70 (56.5) NA
Level of evidence: moderate
The certainty of evidence is downgraded due to imprecision
Table 8. Outcome 6: POEM (Change in POEM total score from baseline)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Mean change from
baseline (95% CI) I
Mean change from
baseline (%) C
Mean difference
compared with placebo (95% CI)
I=intervention; C=comparison; CI=confidence interval
«Simpson EL, Sinclair R, Forman S ym. Efficacy and ...»3 Abrocitinib 100 mg, no concomitant TCS allowed
(153 /70)
12 -6.8 (-8.0 – -5.6) -3.7 (-5.5 – -1.9) -3.1 (-5.2 – -0.9)
Abrocitinib 200 mg, no concomitant TCS allowed
(153//70)
12 -10.6 (-11.8 – -9.4) -3.7 (-5.5 – -1.9) -6.9 (-9.0 – -4.7)
«Bieber T, Simpson EL, Silverberg JI ym. Abrocitini...»4 Abrocitinib 100 mg, concomitant topical treatment allowed (238 /131) 12 -9.6 -5.1 NA
Abrocitinib 200 mg, concomitant topical treatment allowed (226 /131) 12 -12.6 -5.1 NA
Level of evidence: moderate
The quality of evidence is downgraded due to imprecision.

References

  1. Meher BR, Mohanty RR, Padhy BM. Efficacy and safety of abrocitinib for the treatment of moderate-to-severe atopic dermatitis: a meta-analysis of randomized clinical trials. J Dermatolog Treat 2022;33:2335-2343 «PMID: 34315323»PubMed
  2. Silverberg JI, Simpson EL, Thyssen JP ym. Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol 2020;156:863-873 «PMID: 32492087»PubMed
  3. Simpson EL, Sinclair R, Forman S ym. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet 2020;396:255-266 «PMID: 32711801»PubMed
  4. Bieber T, Simpson EL, Silverberg JI ym. Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis. N Engl J Med 2021;384:1101-1112 «PMID: 33761207»PubMed