Table 1 Consensus statements

Scope of application

1 A

Strategies of the PRO-KIND FMF project group apply for patients with clinically diagnosed FMF.

16/17

n.a.

n.a.

Diagnosis

2 A

The clinical diagnosis of FMF typically includes short-lasting recurrent fever episodes and increased inflammatory markers. Additionally, in most patients signs of serositis are present.

17/17

4

C

2B

Genetics play an important role in the diagnosis of FMF. The interpretation of the test results has to take into account the nature of the genotype (confirmatory, consistent, inconclusive or no variant) as well as the clinical phenotype.

17/17

2a

B

2 C

If the diagnosis is unclear, successful use of colchicine can confirm the suspected diagnosis after a sufficiently long observation period with persisting symptoms (e.g. 3–6 months).

17/17

1b-

B

2D

A positive family history can support the clinical diagnosis of FMF.

15/15

2b

B

Differential diagnosis

3 A

In young children with non-confirmatory genotype, FMF diagnosis should be questioned and differential diagnoses such as PFAPA syndrome and age-related physiological susceptibility to infections should be considered.

16/17

3b

B

3B

In unclear cases, further investigations (e.g. genetics) should be performed to identify other possible causes.

13/13

5

D

Treatment targets

4 A

The ultimate treatment goal in FMF is to reach complete control of unprovoked attacks, to minimise subclinical inflammation in between attacks and to prevent damage.

15/16

2b

C

4B

Treatment response should be evaluated every 3–6 months. Treatment efficacy should be evaluated by a composite of parameters according to Fig. 1.

16/16

5

D

4 C

The physician’s and patient’s judgment should be considered to assess the activity and severity of the disease.

16/16

5

D

Colchicine treatment

5 A

Treatment with colchicine should be started as soon as a clinical diagnosis is made due to its effective control of disease activity independently of the patient’s age.

16/16

1a-

A

5B

A starting dose of ≤ 0.5 mg/day (for children < 5 years of age), 0.5-1.0 mg/day (for children 5–10 years of age), or 1.0-1.5 mg/day (for children > 10 years of age) should be administered orally. Colchicine dosage should be increased in a stepwise fashion (e.g. 0.25 mg or 0.5 mg/step) up to a maximum of 2.5 mg/day to control disease in patients who do not clinically respond to the standard dosage (according to Paediatrics, 2007). Colchicine application twice or three times daily may be helpful to avoid gastrointestinal adverse events.

16/16

1b

A

5 C

The persistence of attacks or of subclinical inflammation represents an indication to increase the colchicine dose up to the maximum tolerated dosage.

16/16

2a

B

Monitoring

6 A

Response to colchicine should be monitored every 3–6 months. Evaluation should include assessment and documentation of side effects (intolerance) and toxicity as well as adherence which should be distinguished from resistance.

16/16

2b

C

6B

Increased inflammatory markers (e.g. CRP, SAA, ESR) in the symptom-free interval can indicate subclinical inflammation and should therefore be measured regularly.

15/16

2b

C

6 C

Monitoring of adverse events of colchicine treatment should initially be performed every 2–3 months. The monitoring interval can be extended to 6 months if the treatment is well-tolerated.

15/15

5

D

6D

Urine analyses for the presence of proteinuria and the determination of blood pressure should be performed regularly in order to detect renal amyloidosis.

15/15

3a

C

Colchicine intolerance / inadequate colchicine response

7 A

An inadequate colchicine effect should be determined by a specialist. Before considering inadequate response, adherence to therapy should be confirmed.

15/15

3b

C

7B

If colchicine intolerance is suspected, consider appropriate diagnostic measures to exclude other differential diagnoses.

15/15

5

D

7 C

If there is colchicine intolerance or inadequate response, existing at least over a period of 3–6 months, the decision to intensify therapy should be made, justified and documented by a specialist.

15/15

5

D

7D

If there is inadequate colchicine response and/or colchicine intolerance, treatment with IL-1 antagonists should be considered. The colchicine medication should be maintained.

14/14

1b

A

7E

When choosing IL-1 antagonists, efficacy, especially in children, frequency of injections and severity of local reactions should be considered. In addition, cost-effectiveness and approval status should be taken into account.

15/15

4

C

7 F

With respect to the treat-to-target strategy, the possibility of on-demand therapy and the possibility of dose reduction / increase in application intervals of biologics can be considered.

15/15

4

C

7G

In the case of persistent arthritis in patients with FMF, the additional administration of non-steroidal anti-inflammatory drugs (NSAIDs), local glucocorticoids and methotrexate and, depending on disease activity, TNF inhibitors should be considered.

14/14

4

C

Colchicine reduction / termination

8 A

If a patient is stable with no attacks for more than 3 years and no elevated APR, dose reduction could be considered after expert consultation and with continued monitoring.

14/14

3b

B

8B

In the presence of a non-confirmatory genotype including heterozygous FMF, colchicine might be terminated in asymptomatic patients. These patients should be followed up regularly.

14/14

3b

B