Table 3 Systemic treatments for AD targeting the JAK-STAT axis

From: The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment

Axis

Target

Drug

Clinical trial (NCT number)

Primary endpoint

Results

Status of investigation

JAK-STAT

JAK1

Abrocitinib

NCT03627767 (JADE REGIMEN, Phase III)

% of participants with loss of response during double blind period (week 40).

% loss of response: 77.5% (abrocitinib 200 mg OL to Placebo DB%), 39.6% (abrocitinib 200 mg OL to abrocitinib 100 mg + Placebo DB), 16.5% (abrocitinib 200 mg OL to abrocitinib 200 mg DB) [147].

FDA approved for the treatment of moderate-to-severe AD in adults (January 2022).

NCT03796676 (JADE TEEN, phase III). In combination with TCSs in adolescents

IGA success and EASI75 at week 12.

IGA success: 46.2% abrocitinib 200 mg vs. 41.6% abrocitinib 100 mg vs. 24.5% placebo.

EASI75: 71.0% abrocitinib 200 mg vs. 68.5% abrocitinib 100 mg vs. 41.5% placebo [61].

NCT03349060 (JADE-MONO1, Phase III) adult and adolescents.

IGA success and EASI75 at week 12.

IGA success: 44% abrocitinib 200 mg vs. 24% abrocitinib 100 mg vs. 8% placebo.

EASI75: 63% abrocitinib 200 mg vs. 40% abrocitinib 100 mg) vs. 12% vs. placebo [62].

NCT03575871 ((JADE-MONO2, Phase III) adult and adolescents.

IGA success and EASI75 at week 12.

IGA success: 38.1% abrocitinib 200 mg vs. 28.4% abrocitinib 100 mg vs. 9.1% placebo.

EASI75: 61% abrocitinib 200 mg vs. 44.5% abrocitinib 100 mg vs. 10.4% placebo [228].

NCT03720470 (JADE COMPARE, phase III) vs. dupilumab, in combination with topical therapy.

IGA success and EASI75 at week 12.

IGA success: 48.1% abrocitinib 200 mg vs. 36.6% abrocitinib 100 mg vs. 36.5% dupilumab vs. 14% placebo.

EASI75: 70.3% abrocitinib 200 mg vs. 58.7% abrocitinib 100 mg vs. 58.1% dupilumab vs. 27.1% placebo [146, 228].

NCT04345367 (Phase III) vs. dupilumab, in combination with topical therapy.

Change in PP-NRS at week 2 and EASI90 at week 4.

Pending.

Upadacitinib

NCT03569293 (Measure Up 1, Phase III) adolescents and adults.

IGA success and achieving EASI75 at week 16.

IGA success: 62% upadacitinib 30 mg vs. 48% upadacitinib 15 mg vs. 8% vs. placebo.

EASI75: 72.9% upadacitinib 30 mg vs. 60.1% upadacitinib 15 mg vs. 13.3% placebo[60].

FDA approved for the treatment of moderate-to-severe AD in patients 12 years of age and older (January 2022).

NCT03607422 (Measure Up 2, Phase III) adolescents and adults.

IGA success and achieving EASI75 at week 16.

IGA success: 52% upadacitinib 30 mg vs. 39% upadacitinib 15 mg vs. 5% placebo.

EASI75: 79.7% upadacitinib 30 mg vs. 69.6% upadacitinib 15 mg vs. 16.3% placebo [60].

NCT03568318 (Ad Up, Phase III) adolescents and adults, in combination with TCSs.

IGA success and achieving EASI75 at week 16.

IGA success: 59% upadacitinib 30 mg vs. 40% upadacitinib 15 mg vs. 11% placebo.

EASI75: 77.1% upadacitinib 30 mg vs. 64.6% upadacitinib 15 mg vs. 26.4% placebo [63].

NCT03661138 (Rising Up, Phase III), adolescents and adults, in combination with TCSs.

Number (%) of participants experiencing adverse events at week 24.

56% in upadacitinib 15 mg; 64% in upadacitinib 30 mg, vs. 42% in placebo group. Acne, herpes zoster infections, anemia, neutropenia, CPK elevations were more frequent in the upadacitinib group [229].

NCT03738397 (Heads Up, Phase III) vs. dupilumab.

IGA success and achieving EASI75 at week 16.

EASI75: 71% upadacitinib 30 mg vs. 61.1% dupilumab [148].

JAK1/2

Baricitinib

NCT03334396 (BREEZE-AD1, Phase III)

IGA success and EASI75 week 16.

IGA success: 16.8% baricitinib 4 mg vs. 11.4% baricitinib 2 mg vs. 4.8% placebo [230].

Approved in Europe and Japan for the treatment of moderate-to-severe AD in adults.

NCT03334422 (BREEZE-AD2, Phase III)

IGA success and achieving EASI75 at week 16.

IGA score of 0/1 success: 13.8% baricitinib 4 mg vs. 10.6% baricitinib 2 mg vs. 4.5% placebo [230].

NCT03334435 (BREEZE-AD3, Phase III)

IGA score of 0/1 at week 16, 36, 52.

Week 16: 45.7% (baricitinib 4 mg) vs. 46.3% (baricitinib 2 mg);

week 68: 47.1% (baricitinib 4 mg) vs. 59.3% (baricitinib 2 mg) [231].

NCT03428100 (BREEZE-AD4, Phase III) in combination with TCSs.

Achieving EASI75 at week 16.

EASI75: 31.5% baricitinib 4 mg vs. 27.6% baricitinib 2 mg vs. 17.2% placebo. Only 4 mg was significant compared to placebo [232].

NCT03435081 (BREEZE-AD5, Phase III)

Achieving EASI75 at week 16.

EASI75: 29.5% baricitinib 2 mg, 12.9% baricitinib 1 mg vs. 8.2% placebo [149].

NCT03559270 (BREEZE-AD6, Phase III)

Achieving EASI75 at week 16.

Pending [233].

NCT03733301 (BREEZE-AD7, Phase III) in combination with TCSs.

IGA success and achieving EASI75 at week 16.

IGA success: 30.6% baricitinib 4 mg, 23.9% baricitinib 2 mg, 14.7% placebo [234].

JAK/SYK

Gusacitinib (ASN002)

NCT03531957 (RADIANT, Phase II)

% Change in the EASI score at week 12.

Submitted and awaiting QC approval [235].

Completed.

NCT03654755 (Phase II)

Number and rate of TEAEs at week 104.

Terminated [236].

Terminated.

  1. The table summarizes the results of the most advanced clinical trials for each drug
  2. CPKs creatine phosphokinases, EASI 75 ≥75% reduction in the EASI score from baseline, IGA Investigator Global Assessment, IGA success clear or almost clear (grade 0 or 1) and at least a two-grade improvement in the IGA score from baseline, OL open-label period, PP-NRS Peak Pruritus Numerical Rating Scale, TEAEs treatment-associated adverse events, QC quality control, TCS topical corticosteroid
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