Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B.

BACKGROUND: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. AIM: To assess whether it is beneficial to undergo a prolonged flare after NA cessation. METHODS: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. RESULTS: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. CONCLUSIONS: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.

A man in his fifties with recurrent urticaria, fever and joint pain. / En mann i 50-årene med tilbakevendende urtikaria, feber og leddsmerter.

BACKGROUND: Schnitzler's syndrome is a rare, acquired and probably underdiagnosed disorder. It is a type of autoinflammatory condition with late onset. CASE PRESENTATION: A man in his fifties had had recurrent urticaria, fever and chronic joint pain during the previous year. After an extensive investigation, no evidence of infection, autoimmune disease or malignancy was found. Blood samples showed moderately elevated SR and CRP, mild thrombocytosis and presence of monoclonal IgM in low concentration (MGUS). The combination of sterile inflammation, joint/muscle pain, urticaria and M-component was consistent with Schnitzler's syndrome. He was placed on a treatment trial with anakinra (interleukin [IL]-1 receptor antagonist) 100 mg x 1 daily, given as a subcutaneous injection. His condition was excellent until one week after the first injection. The initial treatment indicated a good clinical effect of IL-1 blockade, but due to the very unpleasant localised side effects (extensive dermatitis), treatment with anakinra was withdrawn, and canakinumab (monoclonal antibody against IL-1ß) was chosen instead. He responded very well to this treatment and experienced no adverse effects. One year after starting treatment, the patient still has an excellent treatment response. INTERPRETATION: Anakinra is the treatment of first choice for this condition, but this case history illustrates that canakinumab can be tried if anakinra is not tolerated by the patient.