Trial Outcomes & Findings for Tofacitinib for Immune Skin Conditions in Down Syndrome (NCT NCT04246372)

NCT ID: NCT04246372

Last Updated: 2025-12-11

Results Overview

Safety as measured by the number of serious adverse events definitely related to tofacitinib treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 47 participants
• Primary outcome timeframe: Baseline to 16 weeks
• Results posted on: 2025-12-11

Participant Flow

Participant milestones

Measure	On Treatment Tofacitinib 5mg oral tablets twice daily for 16 weeks.
Overall Study STARTED	47
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	On Treatment Tofacitinib 5mg oral tablets twice daily for 16 weeks.
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1
Overall Study Protocol Violation	2
Overall Study Physician Decision	1

Baseline Characteristics

Median IFN score with IQR was calculated for 39 participants who completed 16 weeks.

Baseline characteristics by cohort

Measure	On Treatment n=47 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks.
Age, Continuous	22 Years n=47 Participants
Sex: Female, Male Female	23 Participants n=47 Participants
Sex: Female, Male Male	24 Participants n=47 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=47 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=47 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=47 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=47 Participants
Race (NIH/OMB) Asian	0 Participants n=47 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=47 Participants
Race (NIH/OMB) Black or African American	2 Participants n=47 Participants
Race (NIH/OMB) White	40 Participants n=47 Participants
Race (NIH/OMB) More than one race	5 Participants n=47 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=47 Participants
Whole Blood Transcriptome Interferon (IFN) Score	5.28 IFN score n=39 Participants • Median IFN score with IQR was calculated for 39 participants who completed 16 weeks.

PRIMARY outcome

Timeframe: Baseline to 16 weeks

Population: All participants who attended Baseline appointment.

Safety as measured by the number of serious adverse events definitely related to tofacitinib treatment.

Outcome measures

Measure	On Treatment n=47 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Number of Serious Adverse Events (SAE) Definitely Related to Tofacitinib Treatment.	0 Serious Adverse Events

PRIMARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom IFN scores were available at Baseline and 16 weeks.

The Interferon Score is a composite molecular measure used to quantify activation of the interferon signaling pathway. Interferon Scores are calculated by summing standardized expression (i.e. (expression value - mean) / standard deviation) of a predefined panel of 16 interferon-stimulated genes, measured by RNA-sequencing of whole blood samples. The resulting composite value provides an integrated measure of interferon pathway activity, with higher scores indicating greater pathway activation. No clinical relevance threshold has been established.

Outcome measures

Measure	On Treatment n=39 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Change in Whole Blood Transcriptome Interferon (IFN) Score	-8.41 Change in IFN score at 16 weeks Interval -11.66 to -5.16

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom IGA scores were collected at Baseline and 16 weeks.

The IGA is used to assess overall changes in severity across five skin conditions (alopecia areata, atopic dermatitis, vitiligo, psoriasis and hidradenitis suppurativa) scored from 0 (clear) to 4 - 5 (very severe).

Outcome measures

Measure	On Treatment n=42 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Change in Investigator's Global Assessment (IGA)	-1.31 Change in score at 16 weeks 95% Confidence Interval 0.5 • Interval -1.76 to -0.86

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom DLQI scores were collected at Baseline and 16 weeks.

The DLQI is used to assess participant-reported impact of skin conditions on self-image, relationships, and daily activities. Possible total scores range from 0-30, with higher scores indicating a more impaired quality of life.

Outcome measures

Measure	On Treatment n=42 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Change in Dermatology Life Quality Index (DLQI)	-2.88 Change in score at 16 weeks Interval -3.75 to -2.01

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom qualifying EASI scores were collected at Baseline and 16 weeks. None of the completed trial participants had qualifying EASI scores for atopic dermatitis.

The EASI is used to assess changes in the extent (area) and severity of atopic dermatitis (eczema). Each of four sites (head, upper limbs, trunk, and lower limbs), are weighted by overall contribution to body surface area and separately scored by using four parameters (erythema, infiltration, excoriations, lichenification), each of which is graded on a severity scale of 0 (none) to 4 (severe), as well as degree of involvement. Possible total scores range from 0-72, with higher scores indicating a more severe involvement.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom qualifying SALT scores were collected at Baseline and 16 weeks.

The SALT is used to assess changes in degree and extent (area) of hair loss due to alopecia areata on the head. Each of four scalp sites (left side, right side, top and back) are weighted by overall contribution to scalp surface area and rated for percent involvement. Possible total scores range from 0-72, with higher scores indicating a larger affected area.

Outcome measures

Measure	On Treatment n=21 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Change in Severity of Alopecia Tool (SALT) Score in Participants With Alopecia	-28.10 Change in score at 16 weeks Interval -39.27 to -16.92

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom qualifying MSS scores were collected at Baseline and 16 weeks.

The MSS is used to assess changes in areas affected by hidradenitis suppurativa. Each of seven sites (right/left axillae, right/left groin, right/left gluteal, other) are scored by number of lesions, distance between lesions, and presence of normal skin between lesions. Possible total scores range up from 0 with no maximum, with higher scores indicating a more severe involvement.

Outcome measures

Measure	On Treatment n=23 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Change in Modified Sartorius Score (MSS) Score in Participants With Hidradenitis Suppurativa	-19.56 Change in score at 16 weeks Interval -32.19 to -6.94

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom qualifying PASI scores were collected at Baseline and 16 weeks.

The PASI is used to assess changes in extent (area) and severity of psoriasis. Each of four sites (head, upper limbs, trunk, and lower limbs) are weighted by overall contribution to body surface area and separately scored by degree of involvement and three additional parameters (erythema, induration and desquamation), each of which is graded on a severity scale of 0 (Not severe) to 4 (very severe). Possible total scores range from 0-72, with higher scores indicating a more severe involvement.

Outcome measures

Measure	On Treatment n=2 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Change in Psoriasis Area and Severity Index (PASI) Score in Participants With Psoriasis	-7.3 Change in score at 16 weeks Interval -28.9 to 14.3

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom qualifying VETI scores were collected at Baseline and 16 weeks. None of the completed trial participants had qualifying VETI scores for vitiligo.

The VETI is used to assess changes in extent (area) of skin affected by vitiligo. Each of five sites (head, trunk, upper limbs, lower limbs, genitalia) are weighted by overall contribution to body surface area and rated for degree of de-pigmentation scale of Stage 0 (normal skin) to Stage 5 (complete de-pigmentation plus significant hair whitening) and percent involvement. Possible scores range from 0-55.5, with a higher score indicating a higher degree of involvement.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: All participants meeting medication compliance criteria and for whom Cytokine scores were collected at Baseline and 16 weeks.

The Cytokine Score is a composite molecular measure used to quantify inflammatory changes. Cytokine Scores are calculated by summing standardized abundance (i.e. (abundance value - mean) / standard deviation) of a predefined panel of four inflammatory cytokines, measured in plasma samples using the Meso Scale Discovery platform. The resulting composite value provides an integrated measure of inflammatory activity, with higher scores indicating a more inflammatory state. No clinical relevance threshold has been established.

Outcome measures

Measure	On Treatment n=39 Participants Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
A Composite Cytokine Score Generated Using the Meso Scale Discovery (MSD) Platform Used to Assess Inflammatory Changes in Plasma.	-2.15 Change in score at 16 weeks Interval -2.81 to -1.49

Adverse Events

On Treatment

Serious events: 1 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	On Treatment n=47 participants at risk Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune-mediated skin conditions in adults with Down syndrome who completed Baseline and 16-week study time points with adequate medication compliance.
Vascular disorders Thromboembolic event	2.1% 1/47 • Number of events 1 • Baseline through 16 weeks.

Other adverse events

Measure	On Treatment n=47 participants at risk Tofacitinib 5mg oral tablets twice daily for 16 weeks Tofacitinib: Treatment with oral Tofacitinib for immune-mediated skin conditions in adults with Down syndrome who completed Baseline and 16-week study time points with adequate medication compliance.
Gastrointestinal disorders Grade 1 Stomach pain	6.4% 3/47 • Number of events 3 • Baseline through 16 weeks.
Gastrointestinal disorders Grade 1 Diarrhea	12.8% 6/47 • Number of events 9 • Baseline through 16 weeks.
Gastrointestinal disorders Grade 2 Diarrhea	8.5% 4/47 • Number of events 4 • Baseline through 16 weeks.
Gastrointestinal disorders Grade 1 Vomiting	25.5% 12/47 • Number of events 15 • Baseline through 16 weeks.
Skin and subcutaneous tissue disorders Grade 1 Rash acneiform	27.7% 13/47 • Number of events 16 • Baseline through 16 weeks.
Skin and subcutaneous tissue disorders Grade 1 Skin and subcutaneous tissue disorders	12.8% 6/47 • Number of events 8 • Baseline through 16 weeks.
Skin and subcutaneous tissue disorders Grade 2 Skin and subcutaneous tissue disorders	8.5% 4/47 • Number of events 4 • Baseline through 16 weeks.
Investigations Grade 2 Neutrophil count decreased	6.4% 3/47 • Number of events 3 • Baseline through 16 weeks.
Investigations Grade 1 Weight loss	12.8% 6/47 • Number of events 7 • Baseline through 16 weeks.
Investigations Grade 1 Weight gain	36.2% 17/47 • Number of events 20 • Baseline through 16 weeks.
Investigations Grade 2 Weight gain	8.5% 4/47 • Number of events 4 • Baseline through 16 weeks.
Respiratory, thoracic and mediastinal disorders Grade 1 Cough	36.2% 17/47 • Number of events 21 • Baseline through 16 weeks.
Respiratory, thoracic and mediastinal disorders Grade 2 Cough	12.8% 6/47 • Number of events 6 • Baseline through 16 weeks.
Respiratory, thoracic and mediastinal disorders Grade 1 Rhinorrhea	36.2% 17/47 • Number of events 30 • Baseline through 16 weeks.
Respiratory, thoracic and mediastinal disorders Grade 1 Productive cough	6.4% 3/47 • Number of events 3 • Baseline through 16 weeks.
Respiratory, thoracic and mediastinal disorders Grade 1 Nasal congestion	34.0% 16/47 • Number of events 26 • Baseline through 16 weeks.
Respiratory, thoracic and mediastinal disorders Grade 1 Sore throat	10.6% 5/47 • Number of events 12 • Baseline through 16 weeks.
Infections and infestations Grade 1 Infections and infestations - COVID-19	12.8% 6/47 • Number of events 6 • Baseline through 16 weeks.
Infections and infestations Grade 2 Infections and infestations - COVID-19	8.5% 4/47 • Number of events 4 • Baseline through 16 weeks.
Infections and infestations Grade 1 Skin infection	8.5% 4/47 • Number of events 4 • Baseline through 16 weeks.
General disorders Grade 1 Fever	14.9% 7/47 • Number of events 11 • Baseline through 16 weeks.
General disorders Grade 1 Fatigue	14.9% 7/47 • Number of events 10 • Baseline through 16 weeks.
Nervous system disorders Grade 1 Headache	8.5% 4/47 • Number of events 6 • Baseline through 16 weeks.

Additional Information

Joaquin Espinosa

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz

Phone: 303-724-7389

Email: joaquin.espinosa@cuanschutz.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place