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Adalimumab

RA patients in treatment with adalimumab (Humira) at 40mg alternate weeks

The primary objective of the study is to evaluate the safety and tolerability of adalimumab (HUMIRA®) treatment, administered both in monotherapy and combined therapy, in rheumatoid arthritis (RA) patients under usual practice conditions.

adalimumab (HUMIRA®)

Ana M Ruiz-Zorrilla, MD

Adalimumab is one of the pharmacological treatments for rheumatoid arthritis (RA) of more recent marketing authorization, and as a result of this, there are only efficacy and safety data from clinical trials with controlled conditions.The study will evaluate the safety and effectiveness of adalimumab in the common clinical practice of RA treatment in Spain, with several types of patients showing concomitant treatments or diseases and compliance. Among the tumor necrosis factor antagonists safety studies, adalimumab safety has been the less investigated in the common clinical practice because of, as a result of its recent marketing, it was not included in the BIOBADASER (Data Base for Biological Products in Spain, Rheumatology Spanish Society), Biologic Products Database of the Spanish Society of Rheumatology ) in which was determined an association between infliximab therapy and the risk of developing active tuberculosis. To ensure the maintaining of the strict common physician practice (no prescription induction), and following the recommendations of the SER (Sociedad Española de Reumatología, Spanish Society of Rheumatology) consensus documents, it will be selected only those patients that were already in treatment with adalimumab (HUMIRA),(except patients involved in clinical studies with Adalimumab), and had shown good response, or those that fulfilled treatment indication in accordance with the SER recommendations and following the Summary of Products Characteristics of adalimumab (HUMIRA).

Main objective

* To evaluate safety and tolerability of adalimumab (HUMIRA) treatment, administered both in monotherapy and combined therapy, in rheumatoid arthritis patients under usual practice conditions.

Secondary objectives

* To evaluate the effectiveness of the adalimumab (HUMIRA) treatment, administered both in monotherapy and combined therapy, in rheumatoid arthritis patients under usual practice conditions in accordance with SER recommendations:
* To evaluate the life quality associated to the adalimumab (HUMIRA) treatment, administered both in monotherapy and combined therapy, in rheumatoid arthritis patients under usual practice conditions.
* To describe the profile of patients who are in treatment with adalimumab (HUMIRA) biological therapy.

Safety and Effectiveness of Adalimumab in Patients Diagnosed With Rheumatoid Arthritis

Safety and Effectiveness of Adalimumab (HUMIRA®) in Patients Diagnosed With Rheumatoid Arthritis (DALI Study)

The safety and tolerability of adalimumab was assessed at each study visit. The overall number of participants experiencing serious adverse events (SAEs), non-serious adverse events (AEs) and AEs that led to discontinuation are presented. The number of participants presenting with any serious or non-serious event at each particular study visit is also reported. Note that for the incidence data participants were counted multiple times if they experienced an adverse event at more than 1 visit. For additional information see Reported Adverse Events.

The DAS 28 index measures disease activity in rheumatoid arthritis and is derived from the number swollen/tender joints, laboratory tests of inflammation, and participant assessment of global health (by marking a 10 cm line from "very good" to "very bad"). Ranges were used to classify participants, with a higher score indicating worse control of disease: Remission (\<= 2.6), Low Disease Activity (\>2.6 to \<=3.2), Moderate Disease Activity (\>3.2 to \<= 5.1) and High Disease Activity (\>5.1). The mean change in DAS 28 score from baseline to final is presented.

The DAS 28 index measures disease activity in rheumatoid arthritis and is derived from the number swollen/tender joints, laboratory tests of inflammation, and participant assessment of global health (by marking a 10 cm line from "very good" to "very bad"). Ranges were used to classify participants, with a higher score indicating worse control of disease: Remission (\<= 2.6), Low Disease Activity (\>2.6 to \<=3.2), Moderate Disease Activity (\>3.2 to \<= 5.1) and High Disease Activity (\>5.1). The percentage reduction of baseline values is presented.

The treating physician was to clinically assess each participant at each study visit and report the number of painful and swollen joints. The mean number of painful or swollen joints for participants evaluated at each time point are presented by subgroup. The number of participants evaluated in each subgroup at each time point are also reported.

Quality of life was assessed using the Health Assessment Questionnaire (HAQ). The HAQ is a self-reported scale used in studies of rheumatoid arthritis to assess areas such as dressing/grooming arising, eating, walking, reach, grip, maintaining hygiene, and daily activities. The global HAQ questionnaire was scored as follows: \<1 = no/mild disability, 1 to 2 = moderate disability, and \>2 = severe disability. An increased score indicates a worsening of the disability. The mean change in global HAQ score from baseline to 12 months is reported (baseline value - final value).

Quality of life was assessed using the Health Assessment Questionnaire (HAQ). The HAQ is a self-reported scale used in studies of rheumatoid arthritis to assess areas such as dressing/grooming arising, eating, walking, reach, grip, maintaining hygiene, and daily activities. The global HAQ questionnaire was scored as follows: \<1 = no/mild disability, 1 to 2 = moderate disability, and \>2 = severe disability. An increased score indicates a worsening of the disability. The percentage change from baseline to 12 months (12-month score minus baseline score divided by baseline score) is presented.

Treating physicians were asked to obtain a structural damage assessment by performing x-rays of the hands and feet approximately 1 year after the previous structural damage assessment that was done prior to the participant entering the study. The number of participants with radiological erosions evaluated at baseline and the 12-month visit are summarized by subgroup.

Abbott

The safety population included all participants who received at least one dose of adalimumab (675 total). While 184 participants experienced a non-serious adverse event, 18 experienced non-serious adverse events that had an incidence greater than 1% and are presented in the Other Adverse Event table.

Participants with rheumatoid arthritis receiving treatment with adalimumab at 40 mg alternate weeks

Adalimumab Treatment

Adalimumab (Humira)

Based on the ITT population minus 5 who did not report their age (586).

Age Continuous

Female

Male

Gender not reported

Sex/Gender, Customized

Spain

Region of Enrollment

The number of years since the participant first received a diagnosis of rheumatoid arthritis. Based on the ITT population minus 91 who did not report the time since first diagnosis (500).

Time from Diagnosis of Rheumatoid Arthritis

Positive for Rheumatoid Factor

Negative for Rheumatoid Factor

Rheumatoid Factor Results Unknown or Missing

The number of participants testing positive or negative for rheumatoid factor. Based on the ITT population (591).

Positivity of the Rheumatoid Factor

Had previous rheumatoid arthritis treatment

No previous rheumatoid arthritis treatment

Whether or not participants had taken medication for rheumatoid arthritis within the last 5 years. Based on the ITT population (591).

Previous Rheumatoid Arthritis Treatment

Global Medical Services

Overall: Experienced a serious adverse event

Overall: Experienced a non-serious AE

Overall: Discontinued from study due to an AE

Incidence: At least 1 AE at Baseline

-- Incidence: At least 1 AE at 1 month

-- Incidence: At least 1 AE at 4 months

-- Incidence: At least 1 AE at 6 months

-- Incidence: At least 1 AE at 12 months

Incidence: At least 1 SAE at Baseline

-- Incidence: At least 1 SAE at 1 month

-- Incidence: At least 1 SAE at 4 months

-- Incidence: At least 1 SAE at 6 months

-- Incidence: At least 1 SAE at 12 months

This analysis was performed in the safety population of all participants who took at least 1 dose of adalimumab (675 participants).

Safety and Tolerability of Adalimumab Treatment. Adverse Events: Medical Occurrence in a Patient or Clinical Investigation Subject Administered a Pharmaceutical Product and Which Does Not Necessarily Have a Causal Relationship With the Treatment

Those participants to whom adalimumab had been prescribed for the first time 4 months or less before the baseline visit were classified as "de novo" participants.

Adalimumab (De Novo)

Participants who had been taking adalimumab for 4 months or longer.

Adalimumab (Treated for Greater Than 4 Months)

Mean change from baseline to 12 months included the ITT population of 310 de novo and 281 participants treated greater than 4 months.

Disease Activity Score (DAS 28) Index Mean Change From Baseline. The Disease Activity Score (DAS) is a Combined Index That Has Been Developed to Measure the Disease Activity in Patients With Rheumatoid Arthritis (RA).

Mean reduction from baseline to 12 months was calculated for the ITT population of 310 de novo and 279 participants treated greater than 4 months.

Disease Activity Score (DAS 28) Index Percentage Change From Baseline. The Disease Activity Score (DAS) is a Combined Index That Has Been Developed to Measure the Disease Activity in Patients With Rheumatoid Arthritis (RA).

Painful Joints at Baseline (n=310 and n =281)

-- At 1 month (n=277 and n=203)

-- At 4 months (n=292 and n=271)

-- At 6 months (n=269 and n=267)

-- At 12 months (n=255 and n=262)

Swollen Joints at Baseline (n=310 and n=281)

-- At 1 month (n=277 and n= 204)

-- At 4 months (n=292 and n=272)

-- At 6 months (n=269 and n=266)

This analysis was conducted in the ITT population of 591 participants who had assessments at each time point. The number of de novo participants and participants treated greater than 4 months who were analyzed at each time point are given in parentheses.

Clinical Evaluation of Rheumatoid Arthritis (RA). Clinical Evaluation in the Inclusion Visit and in Each One of the Study Visits.

The analysis was conducted for participants who had both baseline and 12-month global HAQ assessments.

Life Quality Assessment Health Assessment Questionnaire (HAQ Questionnaire) Mean Change From Baseline.

Adalimumab (Treatment for Greater Than 4 Months)

Life Quality Assessment Health Assessment Questionnaire (HAQ Questionnaire) Percentage Change From Baseline.

Total number evaluated or not reported at Baseline

a) Radiological erosions present

b) Radiological erosions not present

c) Radiological erosions unknown

Total evaluated or not reported at 12 months

Those participants to whom adalimumab had been prescribed for the first time four months or less before the baseline visit were classified as "de novo" participants.

Adalimumab (Treated for Greater Than 4 Months

This analysis was conducted in the intent-to-treat population (591 participants total).

Radiological Evaluation of Rheumatoid Arthritis (RA).

Overall Study

Osteoarthritis

syringes for injections under cutaneous dose = 40mg vol = 0.8 ml

Adalimumab (Humira®)

Placebo

Xavier Chevalier, PU-PH

Digital osteoarthritis (DO) which affects the interphalangeal joints and the Metacarpophalangeal (MCP) of the thumb is a common disease, the prevalence of which increases with age (36% of the population aged over 70). Certain forms of DO with clinical manifestations involving inflammatory features are particularly refractory to usual treatments (analgesics, NSAIDs, braces and local injections). The mechanism of osteoarthritis involves two major cytokines: interleukin-1 beta and tumor necrosis factor alpha. TNF alpha is particularly involved in the inflammation process.

The aim of the present study is to study the efficacy of TNF alpha blockers (2 injections of adalimumab compared to placebo injections in patients with severe and refractory hand osteoarthritis.

We hope that such new therapeutic option may induce substantial pain relief.

Objective: To demonstrate the efficacy of two subcutaneous injections of anti-TNF alpha (adalimumab) in patients with DO refractory to usual treatments (NSAIDs - analgesics).

Design: Randomized placebo-controlled multicenter (20 sites (amendment 18/12/2008)) trial

Trial duration: 6 months follow-up per patient, total trial duration: 12 months

Number of patients: 84(up)

Dose of administration: Two subcutaneous injections separated by a 2-week interval of either adalimumab or placebo. Therapeutic precautions inherent to the prescription of anti-TNF alpha are based upon those recommended in rheumatoid arthritis. With only two injections of anti-TNF alpha, the risk of complications (infectious in particular) inherent to the anti-TNF alpha appears to be extremely slight.

Patient selection: Patients with digital osteoarthritis (DIP and PIP) according to American College of Rheumatology (ACR) criteria (with a recent X-ray, less than 6 months, of the hands, showing signs of digital osteoarthritis), symptomatic for more than 3 months (at least three finger joints) and scored more than 40 mm on a pain visual analog scale (VAS) despite use of a level 1 analgesic (acetaminophen: 4 g daily) andNSAIDs. Main Exclusion criteria are contraindications to anti-TNF alpha according to international guidelines.

Methods: Patients will be seen at a screening visit, then during treatment administration (W0 and W2) and at follow-up visits: W6, 10, 14 and 26. NSAIDs will be stopped at the time of screening.

Efficacy evaluation: The efficacy endpoint is improvement in pain on a pain VAS at different times of assessment (primary endpoint at W6). A more than 50% improvement, in comparison with baseline, will be considered to be significant. Secondary endpoints are: number of tender joints, number of swollen joints, morning stiffness, global assessment of handicap by patient, global assessment of handicap by physician, the DREISER'S algofunctional index, Cochin hand index, weekly evolution of pain ( patient record), and recording of analgesic use (acetaminophen or NSAIDs).

Statistical data: Statistical analysis will be performed on the inter-group difference in the intention-to-treat population. khi-2 will be used only for criteria number 1.

Anticipated result: Significant superiority of adalimumab over placebo which would provide a therapeutic solution in difficult-to-treat patients with hand OA.

Efficacy Study of an Anti-Tumor Necrosis Factor (TNF) Alpha Agent in Patients With Hand Osteoarthritis

Randomized Double Blind Placebo-controlled Trial of the Efficacy of an Anti-TNF Alpha Agent (Adalimumab, Humira®) in Patients With Incapacitating Hand Osteoarthritis Refractory to Usual Treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Effectiveness of Adalimumab in Patients Diagnosed With Rheumatoid Arthritis	NCT01078571	Rheumatoid Arth...	adalimumab (HUM...	18 Years -	Abbott
Efficacy Study of an Anti-Tumor Necrosis Factor (TNF) Alpha Agent in Patients With Hand Osteoarthritis	NCT00597623	Hand Osteoarthr...	Adalimumab (Hum... Placebo	40 Years - 80 Years	Assistance Publique - Hôpitaux de Paris
Safety and Effectiveness of Adalimumab in Patients Diagnosed With Rheumatoid Arthritis	NCT01078571	Rheumatoid Arth...	adalimumab (HUM...	18 Years -	Abbott

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