Background/Purpose: Familial Mediterranean Fever (FMF) is the most prevalent episodic fever syndrome with more than 100.000 affected individuals worldwide. Colchicine is the established first-line therapy to control disease activity, to achieve remission and to prevent secondary amyloidosis, a significant complication of an inadequately controlled disease and the major cause of mortality in FMF patients. One third of patients with FMF are non- or only partial responders to colchicine and therewith call for experience with other immunosuppressive agents in FMF. Here, we present the first case series of five patients with Familial Mediterranean Fever (FMF) refractory to treatment with colchicine and/or anakinra, who have been switched to monthly treatment with tocilizumab.

Methods: Up to date, eight FMF-patients have been screened for receiving tocilizumab because of inadequate clinical and/or serological response to colchicine and inadequate response or intolerance of anakinra. Treatment has been started in five FMF-patients and is administered with 8 mg/kg bodyweight tocilizumab every 28 days. Colchicine was continued in four patients and discontinued in one patient. Treatment with anakinra, previously given in two patients, was discontinued.

Results: Three patients showed a good clinical and serological response to tocilizumab. In these patients remission of FMF symptoms was achieved with the first application of tocilizumab. A normalization of SAA- and CRP-level was documented after the first application of tocilizumab in one patient and after the third application in another patient. The therapy was well tolerated in four patients with no relevant side effects (one uncomplicated urinary tract infection). In one patient with no acute FMF-attack after the first application of tocilizumab, the therapy had to be discontinued because of an anaphylactic reaction during the second infusion. The first treated patient achieved prolonged remission with tocilizumab-treatment and has been switched back to colchicine alone for maintenance therapy after the ninth infusion. He still is in remission, now 18 months after initiation of tocilizumab therapy. Patient 2 is still on tocilizumab. The request for a self-administerable drug led to a switch back to anakinra after the third infusion of tocilizumab in patient 3. Only patient 4 did not respond to tocilizumab and showed persistent arthralgia and a relapse with abdominal pain after the third infusion. The non-responding patient and the patient with the anaphylactic reaction were switched to anakinra. Three additional patients have currently been scheduled for start of tocilizumab therapy in the nearest future. 

Conclusion: This is the first documentation of a case series of successful treatment of FMF with tocilizumab. Of note, interference with IL-6 activity did not only result in complete clinical remission in three of the five patients previously resistant to immunosuppressive therapy, but also in complete serological remission as indicated by normalization of SAA 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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/familial-mediterranean-fever-inhibition-of-il-6-signalling-as-a-new-therapeutic-option-in-a-frequent-autoinflammatory-syndrome/