Background/Purpose:

Interleukin-1 (IL-1) inhibition was found to be an effective, yet very expensive treatment option for children with clinically and genetically defined autoinflammatory diseases (AID). However, patients suffering from unclassified AIDs with mild to moderate disease activity in the absence of a pathogenic mutation commonly have no access to these treatment options. The aim of this study was to explore the efficacy and safety of colchicine monotherapy in children with AIDs without pathogenic mutations.

Methods:

A single center prospective cohort study of consecutive AID patients ages <18 years without pathogenetic mutations, who were treated with colchicine monotherapy was conducted between January 2009 and February 2018. Patients were included, if they had mild to moderate clinical disease activity and raised inflammatory markers (CRP > 0.5mg/dl, SAA >10 mg/l). Patients were excluded, if they had intolerance to colchicine, elevated liver enzymes > 3x ULN, amyloidosis or other AID related organ damage. Baseline variables included demographics, clinical features, laboratory markers, flare details and overall disease activity. Primary outcome was treatment response at 6 month. Complete response was defined by Physician Global Assessment (PGA) VAS < 2 plus normal inflammatory markers (CRP, SAA), partial response was defined as PGA VAS ≥2 – ≤5 and low normal inflammatory markers (CRP<5mg/dl, SAA <50mg/l). Secondary outcomes included flare characteristics (intervals, duration), toxicity and dose adjustment.

Results: A total of 33 patients were included, 13 girls and 20 boys; median age at start of therapy was 3.8 years (0.8 – 12.6). Clinical diagnoses included PFAPA (14), mutation-negative FMF (9), CAPS with low-penetrance NLRP3-variants (8) (2 V198M, 6 Q703K) and unclassified AID (2). Overall, recurrent fever was the leading symptom, mostly associated with arthralgia and myalgia. On colchicine, the median disease activity decreased from 4 at baseline to 2 at 6 months, median SAA-levels dropped from 74.5 to 4.4 mg/l, CRP from 2.9 to 0.06 mg/dl. Flare frequency was significantly reduced, as was flare duration. Overall, 73% of children responded to Colchicine therapy, complete response was documented in 21%, partial response in 52% at 6 months. The colchicine dose was increased in 79% of children. At last follow-up, 67% had a sustained response to Colchicine. Adverse events included abdominal pain and diarrhea seen in 42%. These appeared to be dose dependent.

Conclusion: Colchicine was an effective and safe treatment option for children with mild to moderately active AIDs. Dose adjustments are frequently required. Gastro-intestinal side effects have to be closely monitored at higher doses.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/colchicine-an-effective-treatment-option-for-unclassified-autoinflammatory-diseases-in-children/