Tocilizumab vs placebo was found to normalize serum amyloid A (SAA) levels and decrease disease activity in patients with Familial Mediterranean Fever (FMF), according to findings published in the Journal of Clinical Medicine.
FMF is an autoinflammatory disease that causes chronic inflammation without the presence of autoantibodies or antigen-specific T-lymphocytes. Symptoms include recurrent fevers, arthralgias, skin lesions, and serositis, as well as increased risk of developing severe amyloidosis leading to organ failure and mortality.
Limited evidence has established the efficacy of tocilizumab in the treatment of FMF, with colchicine as the only available pharmacologic treatment for the condition.
Researchers in Germany conducted a 32-week, multicenter, randomized, placebo-controlled, double-blinded trial (TOFFIFE study; ClinicalTrials.gov Identifier: NCT03446209) at 5 German centers to evaluate the efficacy of tocilizumab in FMF.
They randomly assigned patients diagnosed with FMF into 2 groups: the intervention group that received 8 mg/kg bodyweight of tocilizumab and the placebo group that received a placebo infusion.
Blood samples were collected from all patients at baseline and at weeks 4, 8, 12, 16, 20, 24, 28, and 32.
Outcome measures included levels of C-reactive protein (CRP, >0.5mg/dL), erythrocyte sedimentation rate (ESR, >20 mm/h), SAA levels (>10 mg/dL), and the score on the 5-point physician’s global assessment of disease activity (PGA, >2).
Of 31 participants included in the study, 25, with a median age of 31 years, were randomly assigned to the treatment or the placebo group. After 16 weeks, 2 patients in the intervention group vs none in the placebo group demonstrated an adequate response to tocilizumab (P =.089).
The researchers did not observe any difference in PGA scores between the 2 groups. When analyzing changes in the FMF disease markers, CRP and SAA levels normalized more frequently in response to tocilizumab compared with placebo (P <.011 and P <.015, respectively). Consequently, tocilizumab demonstrated the potential to achieve an important treatment goal of effective FMF treatment by preventing organ failure and mortality secondary to amyloidosis.
Overall, patients in the tocilizumab vs placebo group experienced more side effects; however, serious adverse events occurred more frequently in the placebo group, including higher rates of infection and increased FMF flares. None of the patients experienced opportunistic infections or death. The most serious adverse event in the tocilizumab group was ileitis, and 1 patient demonstrated increased liver enzymes, which is a known side effect of tocilizumab.
Study limitations included the small number of patients, the high drop-out rate, poor adherence to the protocol, and failure to use more precise laboratory biomarkers. The researchers noted the high drop-out rate and the smaller percentage of patients with a good response to tocilizumab, which lowered the evidence-based impact of the study’s findings.
“As the prevention of amyloidosis is a major treatment goal in FMF, the normalization of SAA levels in [tocilizumab]-treated patients is essential.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Henes JC, Saur S, Kofler DM, et al. Tocilizumab for the treatment of Familial Mediterranean Fever – a randomized, double-blind, placebo-controlled phase II study. J Clin Med. 2022;11(18):5360. doi:10.3390/jcm11185360