Table 5 Studies and case reports that discussed the use of toclizumab in FMF

Fujikawa et al. [110]

A 19-year-old female presented with fever, a sore throat, polyarthralgia, and fever-associated skin rashes lasting a couple of days. Inflammatory markers were elevated. Patient was heterozygote for MEFV gene mutation. Steroid and methotrexate didn’t improve the patient’s symptoms.

TCZ treatment was combined with the steroid and methotrexate therapy. The patient’s symptoms, including skin rash, disappeared promptly, so steroid and methotrexate treatment were tapered and then stopped. TCZ was then stopped. Patient remained symptom free for 4 months when he had a relapse managed by colchicine.

Yilmaz et al. [113]

11 patients who had AA amyloidosis secondary to FMF with renal involvement and were treated with TCZ. Before TCZ therapy, all the patients had been using colchicine and an angiotensin receptor blocker or angiotensin converting enzyme inhibitor for at least 3 months without significant response.

Among the 11 patients, 10 patients did not experience any attack during the course of treatment, and no major adverse events were observed. Even though 8 patients had the decreased level of the proteinuria after treatment, there was no case confirmed the reduction of deposition of amyloid in any organ.

Hamanoue et al. [111]

A 51-year-old Japanese man with suspected FMF had periodic fever with abdominal pain, polyarthritis, and nephropathy. FMF was diagnosed by mutation analysis of the MEFV gene. AA amyloidosis was diagnosed by renal and gastric biopsy. Colchicine was administered, but his arthritis persisted, and serum creatinine increased.

Tocilizumab was administered on a monthly basis. Both arthritis and abdominal pain subsided rapidly, and CRP decreased. After 2 years, his serum creatinine was decreased and proteinuria was improved. Repeat gastric biopsy showed a marked decrease of AA amyloidosis.

Umeda et al. [112]

A 64-year-old Japanese woman had been treated with prednisolone for 7 years for undiagnosed recurrent fever and myalgia. She had elevated liver enzymes and inflammatory markers. A muscle biopsy of left quadriceps revealed the infiltration of neutrophils into the fascia as well as vascular endothelium of fascia. She was hetrozygote for the MEFV gene mutation. Patient was stable on colchicine for 5 months when she had a relapse.

Since the initiation of this TCZ treatment, the FMF attacks of fever and myalgia have been completely inhibited for 9 months.

Nikiphorou et al. [114]

A 20-year-old man with a history of chronic recurrent multifocal osteomyelitis, aseptic multiphasic disseminating encephalomyelitis, and a single mutation in the MEFV gene. Despite corticosteroids, adalimumab, colchicine, mycophenolate, and hydroxyxhloroquine normocytic anaemia and high acute phase response persisted.

A trial of anakinra resulted in only partial clinical response, leading to tocilizumab as the next treatment choice. This resulted in rapid clinical and biochemical improvement. After 5 years with ongoing tocilizumab and colchicine he remained well, with normal CRP and amyloid levels.

Nikiphorou et al. [114]

An 18-year-old man had multiple admissions for meningoencephalitis, pyrexia, and anemia. Genetic testing revealed heterozygosity for the MEFV gene.

Sirolimus was unsuccessful in controlling symptoms, leading to a trial of tocilizumab which resulted in suppression of CRP and amyloid to normal levels and enabled steroid withdrawal.

Aikawa et al. [115]

A 53-year-old man with recurrent episodes of large joint pain and a low-grade fever at irregular intervals for 16 years developed right knee and ankle arthralgia, watery diarrhea, and abdominal pain. Following an ileum and colon biopsy, he was diagnosed with gastrointestinal amyloidosis. FMF was suspected, and colchicine was administered colchicine; his symptoms subsequently improved. The patient had atypical FMF. Colchicine was stopped because of alopecia.

Remission was maintained by tocilizumab therapy. In addition, the amyloid deposition in the ileum and colon disappeared.