Table 5.

Points to consider for the monitoring of CAPS, TRAPS, MKD and DIRA

		LoE	GoR	LoA (%)
25	Disease activity and burden of disease should be monitored regularly depending on disease activity and severity, often requiring a multidisciplinary team. • Symptom control can be monitored with validated tools that asses disease-specific symptoms, with patient-reported outcome and quality of life assessments and by recording missing school or workdays. • The frequency of the follow-up evaluations should be tailored to disease severity and clinical needs.	5	D	9.7±0.6
26	Growth and development of children should be monitored at each visit	5	D	9.9±0.3
27	Systemic inflammation should be monitored by following inflammatory markers, including peripheral neutrophilia, CRP and ESR. SAA and S100 protein may be used as inflammatory markers where available.	5	D	9.8±0.5
28	Systemic inflammation may predispose to the development of amyloidosis, and patients should be monitored for the development of amyloidosis by monitoring proteinuria and microalbuminuria.	5	D	9.8±0.5
29	Physicians should be aware of the increased risk of infections in patients with IL-1 targeted therapy, including respiratory tract infections with Streptococcus pneumoniae and skin infections due to Staphylococci.	1	B	9.8±0.4
30	Patients should receive immunizations, in particular live-attenuated vaccines, in accordance with their regional policy, prior to beginning anti-IL-1 targeted therapy when possible.	5	D	9.2±1.4
CAPS Specific
31	Monitoring of organ damage should be established based on disease manifestations and can include monitoring of hearing loss, eye disease, aseptic meningitis, CNS disease and bone disease.	5	D	9.7±0.6
32	Patients with CNS and/or bone involvement should be assessed for developmental delay, the development of bone deformities and limb-length discrepancies	5	D	9.7±0.6
DIRA Specific
33	Normalization of acute phase reactants and absence of inflammatory skin and bone findings is required to determine the adequate dose of IL-1 blocking treatment, and to monitor disease activity long-term.	5	D	9.5±0.8

CAPS, cryopyrin-associated periodic syndromes; TRAPS, tumor necrosis factor receptor associated periodic syndrome; MKD, mevalonate kinase deficiency; DIRA, deficiency of the IL-1 receptor antagonist; LoE: 1a: systematic review of randomized controlled trials (RCTs); 1b: individual RCT; 2a: systematic review of cohort studies; 2b: individual cohort study (including low-quality RCT); 3a: systematic review of case-control studies; 3b: individual case-control study; 4: case-series (and poor-quality cohort and case-control studies); 5: expert opinion without explicit critical appraisal, or based on physiology, bench research or ‘first principles’;GoR: A: based on consistent level 1 studies; B: based on consistent level 2 or 3 studies or extrapolations from level 1 studies; C: based on level 4 studies or extrapolations from level 2 or 3 studies; D: based on level 5 studies or on troublingly inconsistent or inconclusive studies of any level; LoA: level of agreement; CNS, central nervous system; CRP, C-reactive protein; CSF, cerebrospinal fluid; CT, computerized tomography; ESR, erythrocyte sedimentation rate; NA, not applicable