A Study to Describe a Group of Spanish Patients With FMF and to Identify Suboptimally Treated Patients With Minimal Disease Activity and Its Impact on Quality of Life

A Retrospective, Non-interventional, Single-center Study to Describe a Spanish Cohort of Patients With FMF and to Identify Suboptimally Treated Patients With Minimal Disease Activity and Its Impact on HRQoL (Health-Related Quality of Life)

A retrospective, non-interventional, single-center study conducted in Spain, based on the collection of data from the medical histories of patients with Familial Mediterranean fever (FMF) diagnosed during childhood from January 2005 to December 2021.

Data from the patients' medical records was collected retrospectively, from the time of diagnosis to the current moment of the patient's enrollment in the study. Patients had a minimum follow-up of 3 months after diagnosis.

Study Overview

• Status: Completed
• Conditions: Familial Mediterranean Fever

• Study Type: Observational
• Enrollment (Actual): 44

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, non-interventional cohort study.

Description

Inclusion criteria:

1. Patients with FMF clinically and/or genetically diagnosed during childhood according to the site's clinical practice.
2. Patients with at least 3 months of follow-up from the date of diagnosis, at the time of their enrollment in the study.

Exclusion criteria:

1. Patients with autoinflammatory disease excluding FMF.
2. Patients with recurrent fever of another etiology (infectious, tumor or other).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
FMF Cohort; Spanish patients diagnosed with FMF during childhood from January 2005 to December 2021.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients per Clinical Characteristic Category	Clinical characteristic categories included: Diagnostic criteria of FMF (symptom associated with FMF, without a proven infectious cause, with a recurrent pattern and/or accompanied by a genetic test suggestive of Mediterranean FeVer gene [MEFV]); Family history of FMF; MEFV genotypes; Phenotypes of interleukin-1 (IL-1) mediated autoinflammatory disease; Diagnosis prior to FMF	Baseline
Clinical Characteristic: Time From FMF Diagnosis to Study Inclusion		Baseline
Clinical Characteristic: Time From the Start of Symptomatology to Study Inclusion		Baseline
Clinical Characteristic: Time From the Start of Symptomatology to FMF Diagnosis		Baseline
Clinical Characteristic: Age at the Start of Symptomatology		Baseline
Number of Patients by Symptomatology	Symptoms included: Abdominal pain; Arthralgia; Myalgia; Articulatory inflammation; Chest pain; Rash; Fatigue; Symptoms compatible with Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA); Other	Baseline, Month 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132
Number of Patients by Characteristics of Relapses (Flares)	Relapse characteristics included: Fever: high (> 38C), low (≤ 38C), no fever; Relapse frequency (<1 or ≥1 relapse per month for 3 months); Presence of triggers; Presence of complications; Flare and non-flare related inflammatory markers: C-reactive protein (CRP), serum amyloid A protein (SAA), and erythrocyte sedimentation rate (ESR); Disease remission	Baseline, Month 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132
Flare and Non-flare Related Inflammatory Marker Levels	Inflammatory markers included CRP and SAA.	Baseline, Month 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132
Flare and Non-flare Related Erythrocyte Sedimentation Rate (ESR)		Baseline, Month 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132
Number of Flares per Month Since Last Visit		Baseline, Month 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132
Flare Duration Since Last Visit		Baseline, Month 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132
Number of Patients With Recurrency of Flares at Diagnosis		Baseline
Number of Patients by Comorbidity	Comorbidities included vasculitis, panniculitis, inflammatory bowel disease, psoriasis, celiac disease, autoimmune disease, other inflammatory diseases, juvenile idiopathic arthritis, multiple sclerosis, attention deficit hyperactivity disorder (ADHD), and other.	Baseline, Month 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132
Number of Patients by Treatment Received Before FMF Diagnosis	Treatments included: Non-steroidal anti-inflammatory drugs (NSAIDs); Corticoids; Colchicine; Anti-IL-1; Other	Baseline
Number of Patients by Treatment Received At Least Once During the Study	Treatments included: Colchicine; Canakinumab; Anakinra; Corticoids; Methotrexate (MTX); Anti-IL-6; Anti-tumor necrosis factor (TNF)	Up to 11 years
Number of Patients by Treatment and Treatment Combinations Used at the end of the Study	Treatments and treatment combinations included: Colchicine; Canakinumab; Anakinra; Corticoids; MTX; Anti-IL-6; Anti-TNF; Colchicine / Canakinumab; Colchicine / Corticoids; Anakinra; Canakinumab; Colchicine / Anti-TNF; Colchicine / MTX / Anti-IL- 6	Up to 11 years
Number of Patients Using Colchicine With Another Treatment at the end of the Study		Up to 11 years
Number of Patients by First Prescribed Colchicine Dose and Age Group		Up to 11 years
Number of Patients by Colchicine Maximum Global Dose and Age Group		Up to 11 years
Number of Patients With a Change in Colchicine Dose		Up to 11 years
Number of Patients by Reason for Stopping Colchicine Treatment and Age Group		Up to 11 years
Number of Patients by Anti-IL-1 Treatment Used at the end of the Study	Anti-IL-1 treatment included canakinumab and anakinra.	Up to 11 years
Number of Patients by Anti-IL-1 Dose at the end of the Study		Up to 11 years
Number of Patients With a Change in Anti-IL-1 Dose		Up to 11 years
Number of Patients With a Change in Anti-IL-1 Treatment	Changes in treatment included: Change of treatment to a treatment of the same family (anti-IL-1); Change of treatment to a treatment of another family	Up to 11 years
Number of Patients by Reason for Stopping Anti-IL-1 Treatment		Up to 11 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients by Last Reported Response to Colchicine Treatment	Responses included: Complete response: absence of clinical manifestations and normal CRP/SAA levels.; Partial response: <1 flare/month or persistent high CRP/SAA levels with maximum tolerated dose of colchicine or partial response with unknown frequency.; Resistant: ≥1 flare/month or persistent high CRP/SAA levels with maximum tolerated dose of colchicine.; Intolerant: intolerance to treatment as reason for stopping colchicine treatment or changing to another treatment.	Up to 11 years
Time to Achieve Response to Colchicine Treatment	Time to achieve first complete response, complete response, and complete response maintenance were measured.	Up to 11 years
Number of Patients With Intolerance to Colchicine Treatment		Up to 11 years
Autoinflammatory Disease Activity Index (AIDAI) Score	The AIDAI is an assessment tool used to evaluate the level of disease activity. The AIDAI for FMF includes 7 variables: fever, abdominal pain, chest pain, arthralgia or myalgia, swelling of the joints, skin rash, and pain relief taken. Disease activity scores are calculated from the daily scores collected in a patient diary completed during flares. Fever is scored as 0 (absent) or present (1), with all other clinical variables scored from 0 (absent) to 3 (severe). Pain relief taken is not included in the disease activity score calculation. A higher total score indicates a higher level of disease activity. AIDAI was used to assess the association between disease activity and colchicine resistance/intolerance, response to canakinumab treatment, pain, fatigue, and quality of life (absenteeism at school during flares, limitation of physical activity, psychological care, and overall health status).	Up to 11 years
Autoinflammatory Disease Damage Index (ADDI) Score	The ADDI is an assessment tool used to evaluate the level of damage caused by autoinflammatory disease. It consists of 18 damage items grouped by organ system: reproductive, renal/amyloidosis, developmental, serosal, neurological, ears, ocular and musculoskeletal damage. Each damage item is defined and assigned a score of 1, 2, or 3, with each organ system having a maximum allowed score. A higher total score indicates a higher level of damage. ADDI was used to assess the association between disease damage and colchicine resistance/intolerance, response to canakinumab treatment, pain, fatigue, and quality of life (absenteeism at school during flares, limitation of physical activity, psychological care, and overall health status).	Up to 11 years
Familial Mediterranean Fever 50 (FMF50) Score	The FMF50 is an assessment tool used to evaluate response to treatment for FMF. It consists of 6 items: Percentage change in the frequency of attacks with the treatment.; Percentage change in the duration of attacks with the treatment.; Patients/parents' global assessment of disease severity.; Physicians' global assessment of disease severity.; Percentage change in arthritis attacks with the treatment.; Percentage change in CRP, ESR, or SAA level with the treatment. An improvement of at least 50% in 5 of the 6 items without worsening in any one item indicates that the patient is responding to treatment. FMF50 was used to assess response to canakinumab treatment and the association between response to treatment and colchicine resistance/intolerance, pain, fatigue, and quality of life (absenteeism at school during flares, limitation of physical activity, psychological care, and overall health status).	Up to 11 years
Number of Patients by Last Response Reported to Anti-IL-1 Treatment During the Study	Responses included: Complete response: absence of clinical manifestations and normal CRP/SAA levels.; Incomplete response: persistent febrile episodes or high CRP/SAA levels; Partial response: <1 flare/month or persistent high CRP/SAA levels with maximum tolerated dose of colchicine or partial response with unknown frequency.; Resistant: ≥1 flare/month or persistent high CRP/SAA levels with maximum tolerated dose of colchicine. Anti-IL-1 treatments included canakinumab and anakinra.	Up to 11 years
Time to Achieve Response to Anti-IL-1 Treatment	Time to achieve complete response and complete response maintenance were measured. Anti-IL-1 treatments included canakinumab and anakinra.	Up to 11 years
Number of Patients With MEFV Mutation by Treatment Response	Response categories included: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Number of Patients Without MEFV Mutation by Treatment Response	Response categories included: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Number of Patients With Mutation in Other Loci by Treatment Response	Response categories included: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Number of Medical Visits of Patients With Scholar Absenteeism During Flares by Response to Anti-IL-1 Treatment	Anti-IL-1 treatments included canakinumab and anakinra. Responses were categorized as follows: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Number of Medical Visits of Patients With Physical Activity Limitations by Response to Anti-IL-1 Treatment	Anti-IL-1 treatments included canakinumab and anakinra. Responses were categorized as follows: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Number of Medical Visits of Patients Requiring Psychological Care by Response to Anti-IL-1 Treatment	Anti-IL-1 treatments included canakinumab and anakinra. Responses were categorized as follows: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Number of Medical Visits of Patients With Presence of Pain by Response to Anti-IL-1 Treatment	Anti-IL-1 treatments included canakinumab and anakinra. Responses were categorized as follows: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Number of Medical Visits of Patients With Presence of Fatigue by Response to Anti-IL-1 Treatment	Anti-IL-1 treatments included canakinumab and anakinra. Responses were categorized as follows: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Visual Analogue Scale (VAS) Score From Clinician Point of View	Patients' overall state of health was assessed using VAS scoring. The VAS is a straight line with a scale ranging from 0 (worst health) to 10 (best health). The clinician marks a point on the line, scoring how they perceive the patient's overall state of health. VAS was used to assess the association between anti-IL-1 treatment response and overall state of health. Anti-IL-1 treatments included canakinumab and anakinra. Treatment response was categorized as follows: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years
Visual Analogue Scale (VAS) Score From Patient Point of View	Patients' overall state of health was assessed using VAS scoring. The VAS is a straight line with a scale ranging from 0 (worst health) to 10 (best health). Patients mark a point on the line, scoring how they perceive their overall state of health. VAS was used to assess the association between anti-IL-1 treatment response and overall state of health. Anti-IL-1 treatments included canakinumab and anakinra. Treatment response was categorized as follows: Respondent: without flares and with normal inflammatory markers in the last 3 months.; Non-respondent: with flare and/or elevated inflammatory markers in the last 3 months.; Partial respondent: did not fulfill some of the criteria for complete response.	Up to 11 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Actual): May 28, 2024
• Study Completion (Actual): May 28, 2024

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Infections; Skin Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Skin Diseases, Genetic; Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases
• Other Study ID Numbers: CACZ885NES01R