Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Necrosis

Psoriasis

Skin Diseases

Skin Diseases, Papulosquamous

Chronic Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Anti-Inflammatory Agents

Vitamins

Methotrexate

Folic Acid

Vitamin B Complex

Adalimumab

Antimetabolites

Enzyme Inhibitors

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Tumor Necrosis Factor Inhibitors

Trace Elements

Folinic Acid

Folate

Vitamin B9

Dosing will be on day 1 and then weekly. For the injections, dosing will occur according to product recommendations. Patients will receive 80mg adalimumab (2 pre-filled syringes, each with 40mg) on day 1, and then 40mg on week 1 and then every 2 weeks (from week 1 through week 15).

Patients will be dosed according to the CHAMPION study in single weekly doses of methotrexate: 7.5mg at week 0, 10mg at week two, and 15mg at week 4 for all patients. For each subject if the PASI did not decrease by at least 50% from baseline (PASI-50) at week 8, dosing will be increased to 20mg per week; the dose will be maintained at 15mg per week if PASI-50 was achieved at week 8. If PASI-50 was not achieved at week 12, dosing will be increased to 25mg per week; the dose will be maintained at 20mg per week if the PASI-50 was achieved at week 12. All patients on methotrexate will also receive a dietary supplement of oral folate (5mg per week). Methotrexate-treated patients will then receive 16 weeks of adalimumab at the end of study.

2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.

Methotrexate-treated patients will then receive 16 weeks of adalimumab at the end of study.

2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.

Adalimumab (Humira)

Alice B. Gottlieb, M.D., PhD.

The objective of this study is to compare the mechanism of action between adalimumab and methotrexate in subjects with psoriasis.

Both methotrexate and adalimumab are FDA-approved drugs for the treatment of moderate to severe psoriasis. The two treatments, methotrexate and adalimumab, both show efficacy for psoriasis, however their profiles differ. In the CHAMPION Study, more adalimumab-treated, moderate to severe psoriasis patients achieved a PASI 75 after 16 weeks compared to those treated with methotrexate (80% vs. 36%). The reason for this difference is poorly understood. No direct comparative mechanism of action studies in psoriasis patients between methotrexate and adalimumab (or any tumor necrosis factor blocker) has been reported.

With etanercept, another tumor necrosis factor blocker, the in vivo mechanism has been studied with some scientific rigor. These studies demonstrate that etanercept down regulates multiple pro-inflammatory pathways (as shown in Table 1 of the protocol).

To date, there are no similar studies with adalimumab or methotrexate.

In order to understand the molecular and cellular basis for the differential clinical efficacy of adalimumab and methotrexate, it is essential to compare their mechanisms of action in psoriatic plaques. Biopsies will be performed, and we will study biomarkers in this proposal with immunohistochemistry, real-time polymerase chain reaction, and gene arrays.

Mechanism of Action Study for Psoriasis

An Investigator-Initiated, Assessor Blinded, Randomized Study Comparing the Mechanism of Action of Adalimumab to Methotrexate in Subjects With Moderate to Severe Chronic Plaque Psoriasis.

A single, long-term follow-up visit will be done for all available subjects for additional pharmacogenetic analysis. The goal in collecting DNA from psoriasis patients is to determine if individual subjects have gene variants associated with increased incidence of psoriasis. The investigators plan on analyzing variants using single nucleotide polymorphism (SNP) analysis by high-throughput DNA sequencing. This patient genetic information may allow us to correctly interpret data collected about gene expression levels in affected or non-affected skin. Additionally genetic typing may lead to cogent personalized health care (PHC) strategies for the identification of psoriasis drug responders/non-responders, patients who achieve durable disease remission post-treatment, and/or pharmacodynamic markers, as examples.

Histologic and Immunohistochemistry endpoints; Relative messenger RNA gene expression (normalized to HARP); and Gene Arrays.

PASI 75 is the percent of subjects who experience an improvement in PASI (Psoriasis Area and Severity Index) score of at least 75% from their baseline PASI score.

The lesion score of a single psoriatic plaque selected at baseline. Total range is 0 - 12 with 0 being clear and 12 representing the most severe disease. The target lesion score is composed of scale, erythema, and induration, each parameter is scored 0 (clear) through 4 (very severe). Totals are summed for target lesion score. S+E+I = TLS

Tufts Medical Center

Dosing will be on day 1 and then weekly. For the injections, dosing will occur according to product recommendations. Patients will receive 80mg adalimumab (2 pre-filled syringes, each with 40mg) on day 1, and then 40mg on week 1 and then every 2 weeks (from week 1 through week 15).

Adalimumab (Humira): 2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.

Patients dosed in single weekly doses of methotrexate 7.5mg at week 0, 10mg at week two, and 15mg at week 4 for all patients. For each subject if the PASI did not decrease by at least 50% from baseline (PASI-50) at week 8, dosing will be increased to 20mg per week; the dose will be maintained at 15mg per week if PASI-50 was achieved at week 8. If PASI-50 was not achieved at week 12, dosing will be increased to 25mg per week; the dose will be maintained at 20mg per week if the PASI-50 was achieved at week 12. All patients on methotrexate will also receive a dietary supplement of oral folate (5mg per week). Methotrexate-treated patients will then receive 16 weeks of adalimumab at the end of study.

Methotrexate: 2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.

Methotrexate-treated patients will then receive 16 weeks of adalimumab at the end of study.

Methotrexate (MTX)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Asian

caucasian

african american

unknown

hispanic

Race/Ethnicity, Customized

United States

Region of Enrollment

Nicole Dumont

CAMP(responders)

CAMP(Non responders)

CCL20 (responders)

CCL20 (non responders)

CXCL1 (responders)

CXCL1 (non responders)

DEFB4A (responders)

DEFB4A (non responders)

IL 17F (responders)

IL 17F (non responders)

IL 17A (responders)

IL 17A (non responders)

IL 23 A (responders)

IL 23A (non responders)

IL 22 (responders)

IL 22 (non rsponders)

IFNG (responders)

IFNG (non responders)

MX1 (responders)

MX1 (non responders)

Biologic Activity Endpoints

Clinical Endpoints for Psoriasis: PASI 75

Additional Gene Analysis (Ongoing)

Clinical Endpoints for Psoriasis: Physician's Global Assessment (PGA) Clear or Almost Clear (PGA 0-1)

Clinical Endpoints for Psoriasis: % Body Surface Area

Clinical Endpoints for Psoriasis: Target Lesion Score

Clinical Endpoints for Psoriasis: Photography Completed

Overall Study

Musculoskeletal Diseases

Immune System Diseases

Joint Diseases

Arthritis

Arthritis, Rheumatoid

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Autoimmune Diseases

Open-label, one arm only. All patients receiving active drug according to recommendations (adalimumab (Humira) 40 mg subcutaneously every other week).

Adalimumab (Humira) 40 mg subcutaneously every other week

Mikkel Østergaard, Professor

Uffe Møller Døhn, M.D

Studies on tumor necrosis factor alpha antagonist (anti-TNF) therapy in rheumatoid arthritis (RA) patients have found that erosive damage may "heal" in some RA patients treated with anti-TNF. Repeated examinations of adalimumab (Humira) treated RA patients, using computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US) and radiography will allow detailed assessment of the extent of bone repair/healing during adalimumab (Humira) therapy.

Studies on tumor necrosis factor alpha antagonist (anti-TNF) therapy in rheumatoid arthritis (RA) patients have found that radiographic erosions scores decreased in some patients. This suggests that erosive damage may "heal" in some RA patients treated with anti-TNF. However, it is not clarified whether the reduced scores are caused by technical issues as observer variation and image acquisition differences. Furthermore, radiography of erosions is a 2D representation of a 3D pathology and therefore not ideal for visualizing healing, if present. Verification of erosion healing under anti-TNF therapy with adalimumab (Humira) by optimal imaging methods, would markedly influence our perception of the effect and potential of adalimumab (Humira) for modifying structural joint damage in RA. Magnetic Resonance Imaging (MRI), allowing high-resolution 3D visualization of bone damage as well as the inflammatory activity in the bone (bone marrow edema/osteitis), is more sensitive for visualization of bone erosions than radiography. Computed Tomography (CT) is a 3D radiographic imaging technique, which is not suited for assessment of inflammation, but can be considered a reference method for assessment of bone damage, due to its direct 3D visualization of calcified tissue. Internationally recommended MRI scoring systems as well as methods for estimation of erosion volumes have been developed, with participation by our research group. Ultrasonography (US), even though less validated, is more sensitive than radiography and comparable to MRI in detecting bone erosions in RA joints. Additionally, US provides visualisation of soft tissue changes and synovitis, using gray-scale and Doppler US.

Repeated MRI, CT, US and radiographic examinations of RA joints with mild to moderate radiographic damage under adalimumab (Humira) therapy will allow detailed assessment of the extent of bone repair/healing during adalimumab (Humira) therapy.

Humira in Rheumatoid Arthritis - Do Bone Erosions Heal?

Can Bone Erosions Heal in Adalimumab (Humira) Treated Rheumatoid Arthritis Patients. An Imaging Study Using Computed Tomography and Magnetic Resonance Imaging.

Abbott

Hvidovre University Hospital

Mikkel Østergaard

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Mechanism of Action Study for Psoriasis	NCT00932113	Psoriasis	Methotrexate Adalimumab (Hum...	18 Years - 85 Years	Tufts Medical Center
Humira in Rheumatoid Arthritis - Do Bone Erosions Heal?	NCT00696059	Rheumatoid Arth... Arthritis Joint Diseases	Adalimumab (Hum...	18 Years - 90 Years	Hvidovre University Hospital

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