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

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

Symptoms included:

• Abdominal pain
• Arthralgia
• Myalgia
• Articulatory inflammation
• Chest pain
• Rash
• Fatigue
• Symptoms compatible with Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA)
• Other

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

Inflammatory markers included CRP and SAA.

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.

Treatments included:

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticoids
• Colchicine
• Anti-IL-1
• Other

Treatments included:

• Colchicine
• Canakinumab
• Anakinra
• Corticoids
• Methotrexate (MTX)
• Anti-IL-6
• Anti-tumor necrosis factor (TNF)

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

Anti-IL-1 treatment included canakinumab and anakinra.

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

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.

Time to achieve first complete response, complete response, and complete response maintenance were measured.

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).

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).

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).

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.

Time to achieve complete response and complete response maintenance were measured. Anti-IL-1 treatments included canakinumab and anakinra.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.