Background With more than 100.000 affected individuals worldwide, Familial Mediterranean Fever (FMF) is the most prevalent episodic fever syndrome. Besides recurrent attacks of fever and painful serositis as typical and life-quality affecting symptoms, the dreaded complication of an inadequately controlled disease is the development of secondary amyloidosis, which is the major cause of mortality in FMF patients. Colchicine is the established first-line therapy to control disease activity, to achieve remission and to prevent secondary amyloidosis. However, about one third of patients with FMF are non- or only partial responders to colchicine and therewith have promoted the experience of other immunosuppressive agents in FMF.
Objectives Here, we present the first case series of five patients with Familial Mediterranean Fever (FMF) refractory to treatment with colchicin and/or anakinra, who have been switched to monthly treatment with tocilizumab.
Methods We report on five patients who have been treated with tocilizumab because of inadequate clinical and/or serological response to colchicine and inadequate response or intolerance of ankinra. Tocilizumab was administered at a dosage of 8 mg/kg bodyweight every 28 days. Colchicin was continued in four patients and discontinued in one patient. Treatment with anakinra, previously given in three patients, was discontinued.
Results Four patients showed a good clinical and serological response to tocilizumab with a significant decrease of serum amyloid A (SAA) levels. Remission of FMF symptoms was achieved in three patients with the first application of tocilizumab. A normalization of increased levels of SAA and CRP was documented after the first application of tocilizumab in one patient and after the third application in another patient (depending on initial SAA levels). The therapy was well tolerated in all five patients with no relevant side effects (one uncomplicated urinary tract infection). In the first treated patient tocilizumab has already been switched back to colchicin alone after the ninth infusion because of complete remission for 6 months. The patient who did not respond to tocilizumab with persistent arthralgia and a relapse of abdominal pain after the third infusion, responded well to a switch of treatment to anakinra. In the other three patients tocilizumab infusions are still continuing with a median treatment duration of four months.
Conclusions This is the first documentation of a successful treatment of FMF with tocilizumab. Of note, interference with IL-6 activity did not only result in complete clinical remission in four of the five patients previously resistant to immunosuppressive therapy, but also in complete serological remission as indicated by normalization of SAA and CRP in two individuals. These data strongly argue in favour of IL-6 as a main inflammatory cytokine in FMF and, thus, as a promising target in this disease.
Disclosure of Interest None Declared
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