Table 4.
Recommendations for the management and treatment strategies of MKD.
| Treatment: | LoE | LoA (1-9) mean ± SD |
|---|---|---|
| Anti-inflammatory treatment | ||
| 1. The mainstay of treatments is with inhibitors of the interleukin-1 (IL-1) pathway, such as canakinumab (registered) or anakinra (off label), to treat and prevent inflammatory episodes. | A | 8,3 ± 1,5 |
| 2. Compared with other autoinflammatory diseases, higher doses of canakinumab may be required to control MKD flares. | A | 8,5 ± 0,7 |
| 3. On-demand IL-1 blockade with anakinra may be considered on a case-by-case basis. | B | 8,2 ± 0,9 |
| 4. NSAIDs may be used to for symptomatic relief of mild disease flares. | B | 8,2 ± 0,9 |
| 5. Short-term glucorticoids can be used to treat disease flares. | B | 8,1 ± 0,9 |
| 6. Consider TNF or IL-6 blockade as potential second-line biologic agents for patients who do not respond adequately to interleukin-1 inhibitors. | B | 7,9 ± 1,0 |
| 7. Statins or bisphosphonates for MKD treatment are not recommended. | C | 8,7 ± 0,5 |
| 8. Allogeneic hematopoietic stem cell transplantation for severe refractory cases of MKD remains a viable therapeutic option but should be balanced against the risks involved. | A | 8,5 ± 0,6 |
| Treat-to-target strategies: | LoE | LoA (1-9) mean ± SD |
| 1. Treat to the following targets: reduced frequency and severity of disease flares; normalization of acute phase reactants; limitation of glucocorticoid toxicity. Growth and patient quality of life are usually optimized if these are achieved. | A | 8,3 ± 0,9 |
| 2. Consider using evaluations and tools such as the autoinflammatory disease activity index (AIDAI), the physician’s global assessment and the patient’s parent global assessment to monitor clinical disease activity, ensuring timely treatment adjustments based on therapeutic efficacy. | A | 8,4 ± 0,9 |
| 3. Regular serological tests (every 3 months as a minimum) of acute phase markers (WCC, CRP, and SAA) should be used to monitor serological disease activity to detect subclinical inflammation. | A | 7,9 ± 1,2 |
| 4. Regular monitoring of urinalysis for microalbuminuria or protein to creatinine ratio is recommended. | A | 7,9 ± 1,4 |
| 5. Monitor growth regularly (every 3-6 months). | A | 8,2 ± 1,1 |
| 6. Consider the escalation of therapy if these targets are not being met. | A | 8,1 ± 1,1 |
| Vaccination: | LoE | LoA (1-9) mean ± SD |
| 1. Patients with MKD should adhere to their vaccination schedule where possible, as the potential risk of a disease flare is outweighed by the serious consequences of vaccine-preventable infections. | A | 8,5 ± 0,7 |
| 2. The vaccination strategy is dictated primarily by the immunomodulatory treatments used, rather than by the disease itself. It is recommended to consult international and national guidelines, specifically in relation to the receipt of live vaccines while on biologic treatment. | A | 7,9 ± 2,1 |
| 3. Before receiving vaccines, patients with MKD should consult with their healthcare provider, ideally a specialist familiar with autoinflammatory diseases, to discuss the benefits and risks associated with vaccination in the context of their condition. | A | 8,2 ± 1,8 |
| 4. In managing flares for MKD patients around vaccination times, NSAIDs rather than glucocorticoids can be specifically suggested for symptomatic relief to avoid significantly dampening the response to vaccines. | D | 7,9 ± 1,7 |
Level of evidence (LoE): A: Level I evidence or consistent findings from multiple studies of levels II, III, or IV; B: Levels II, III, or IV evidence and findings are generally consistent; C: Levels II, III, or IV evidence, but findings are inconsistent; D: Level V evidence: little or no systematic empirical evidence; Level of agreement (LoA).