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.
| 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 | |
| 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
| 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. | |||||
| 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). |
|||||
| 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. | |||||
| 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. | |||||
| 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 |
|||||
| 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. |
|||||