Background/Purpose: Yao syndrome (YAOS, OMIM 617321), formerly termed nucleotide-binding, oligomerization domain 2(NOD2)-associated autoinflammatory disease, is characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. The disorder is associated with specific NOD2 variants. YAOS is not uncommon, yet effective drugs remain limited due to its recent identification. This study aimed at examining the therapeutic utility of canakinumab, a monoclonal antibody against interleukin-1β for the disease.

Methods:

In this retrospective analysis of prospectively designed single center study approved by the Institutional Research Board, 6 adult Caucasian patients that were enrolled fulfilled the diagnostic criteria for YAOS as confirmed by molecular analysis. These patients naïve to biologics received subcutaneous injections of canakinumab 150 mg every 4 to 8 weeks for 2 to 12 months. The primary end point was the change of overall clinical response evaluated by patient’s global assessment at week 1, 2, 3 and 4. Secondary end points included changes in each of the major signs and symptoms using modified Schnitzler activity score on a scale of 0-4. Inflammation markers and drug adverse reactions were recorded including routine laboratory tests.

Results:

All 6 patients receiving canakinumab reported overall clinical improvement with a mean change of 78% as compared with that before the drug administration. Patients noted improvement from day 7 following the injection with peak effect around day 14 to 21, and the improvement generally lasted up to 4 weeks. Patients felt even more symptomatic relief with more drug dosing over time. The results of the constituent signs and symptoms at day 14 after the biologic administrations are summarized in Table 1, and there was 78% improvement in fever and approximately 70% in each of the other major phenotypes, such as rash, arthritis, sicca-like and gastrointestinal symptoms. Three out of the 6 patients had elevated inflammation markers that normalized after canakinumab. Adverse events were minimal, including minimally elevated liver enzymes in one patient.

Table 1. Demographics, Scores and Changes in Major Constituent Manifestations in YAO Syndrome Patients Receiving Canakinumab

Note: Dx: diagnosis; CAN: Canakinumab; Scores are based upon a scale of 0-4 with 4 being the most severe; B/A: before and after Canakinumab injections; Improvement % is computed based upon the score changes before and after treatment divided by the scores

before the treatment; SD: standard deviation.

Conclusion:

In this study, canakinumab was effective in patients with YAOS, and thus clinical trial of canakinumab may be warranted as a therapeutic option for this disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/therapeutic-value-of-canakinumab-in-patients-with-yao-syndrome/