BACKGROUND: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1β (IL-1β), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.
OBJECTIVE: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF.
METHODS: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF.
RESULTS: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF.
CONCLUSIONS: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

OBJECTIVE: To systematically evaluate the efficacy of subcutaneous tocilizumab in the treatment of patients with severe COVID-19 and provide evidence for the rational use of subcutaneous tocilizumab in patients with severe COVID-19.
METHODS: This meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched the Cochrane Library, PubMed, Embase, CNKI, SinoMed, and Wanfang Medical Network electronic databases up to 11 January 2023 to identify relevant studies. To obtain the most recent clinical studies of subcutaneous injection of tocilizumab for the treatment of patients with severe COVID-19, we also searched the preprint platforms medRxiv and ChinaXiv. Furthermore, we searched ClinicalTrials.gov for relevant unpublished studies. The studies were screened based on the PICOS principle. The included studies were classified and evaluated for quality based on research type. The RevMan 5.3 software was used to conduct the meta-analysis, and a descriptive analysis was performed to examine relevant outcome indicators.
RESULTS: Five observational studies were obtained, involving a total of 498 patients (240 patients in the subcutaneous injection group and 258 patients in the intravenous injection group). All of the studies were of the highest quality. The meta-analysis of the included studies revealed that the mortality rate of patients who received subcutaneous tocilizumab to treat COVID-19 was not significantly higher than that of the intravenous injection group [23.3% (45/193) vs. 18.4% (39/212), RD = 0.06, 95% CI = - 0.01 ~ 0.13, P = 0.11]. Furthermore, there was no significant difference in the proportion of patients requiring mechanical ventilation between the two groups [24.5% (35/143) vs. 22% (35/159), RD = 0.03, 95% CI = - 0.07 ~ 0.12, P = 0.56].
CONCLUSIONS: The meta-analyses do not provide evidence that subcutaneous and intravenous tocilizumab formulations for the treatment of severe COVID-19 infection differ regarding their effectiveness. Considering that the meta-analyses cannot replace an appropriately powered non-inferiority study, subcutaneous formulations still need to be used with caution and only when intravenous formulations are in short supply. At present, there is a lack of randomized controlled trials of subcutaneous injection of tocilizumab for the treatment of severe COVID-19, and more clinical research should be conducted.

BACKGROUND: We present a rare case of NeuroBehcet\'s-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet\'s. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic.
METHODS: The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet\'s disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity.
METHODS: We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later.
CONCLUSIONS: As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.

OBJECTIVE: Still\'s disease is a rare autoinflammatory disorder characterized by systemic inflammation, fever, rash, and arthritis. The term \"Still\'s disease\" covers the pediatric subtype systemic Juvenile Idiopathic Arthritis (sJIA) and adult-onset Still\'s disease (AOSD), which affects adults. Biological drugs, including anti-interleukin-1 agents anakinra, canakinumab, rilonacept, and the interleukin-6 antagonist tocilizumab, are used in the management of Still\'s disease.
METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials, and the study protocol was registered in PROSPERO (CRD42023450442). MEDLINE, EMBASE, and CENTRAL were screened from inception until September 17, 2023. We included patients with Still\'s disease who received placebo or biological drugs: anakinra, canakinumab, rilonacept, or tocilizumab. The primary efficacy and safety outcomes were achievement of ACR50 response and occurrence of serious adverse events, respectively. The interventions were ranked using rankograms and SUCRA values.
RESULTS: Nine trials with 430 patients were included. All biological drugs were associated with greater odds of ACR50 response compared with placebo. There was no statistically significant association between biological drugs and serious adverse events. The multivariate meta-analysis found no difference between biological drugs. As per SUCRA rankings, anakinra was the most effective and safe option with respect to ACR50 response and occurrence of serious adverse events.
CONCLUSIONS: This is the first systematic review and meta-analysis to assess the efficacy and safety of biological drugs in pediatric and adult patients with Still\'s disease. Biological drugs were effective in achieving ACR response and demonstrated a low adverse event profile in the management of Still\'s disease.

Giant Cell Arteritis (GCA), also known as Temporal Arteritis, is a type of large vessel vasculitis primarily affecting the elderly population. It typically manifests with headaches, visual impairment, and jaw claudication. Although third nerve palsy as the primary presentation of GCA is rare, it has been reported in previous instances. In this report, we describe the case of a patient presenting with pupil-sparing third nerve palsy, ultimately diagnosed with GCA, and successfully managed with steroids and tocilizumab. A lady in her 80s with past medical history of well-controlled hypertension, bladder cancer in remission, a twenty-pack year smoking history, cervical and lumbar spine stenosis, and recent immunizations presented with acute onset of right-sided pupil-sparing third nerve palsy. Labs were pertinent for an elevated ESR and CRP. Brain imaging was without acute abnormalities. A temporal artery biopsy established evidence of healed arteritis and a diagnosis of GCA was made. The patient was treated with pulse-dose steroids followed by an oral steroid taper and tocilizumab. At one month follow-up, there was partial resolution in her ophthalmoplegia. We underscore the importance of considering temporal arteritis as a potential cause of third nerve palsy in the elderly before attributing it solely to microvascular ischemia, particularly in patients with constitutional features. Additionally, in our comprehensive literature review, we aim to consolidate the existing data from similar presentations, shedding light on the clinical manifestation and disease trajectory.

Cogan syndrome (CS) is a rare systemic vasculitis characterized primarily by nonsyphilitic interstitial keratitis and vestibular and auditory dysfunction. In this article, we report the case of a 31-year-old male diagnosed with CS for 1 year. He was admitted to the hospital with fever, dizziness, headache, tinnitus, and hearing loss. After being treated with glucocorticoids, cellular immunosuppressants, and infliximab therapy, his symptoms were greatly relieved except for hearing loss. Then, he attempted to use tocilizumab (TCZ) which was ultimately effective in controlling the auditory dysfunction. In addition, we found 4 cases of TCZ for CS through a literature review and compared them with our patient. Although glucocorticoids are still the first-line treatment for CS, TCZ therapy provides fresh hope for patients who have refractory hearing impairment with hormone resistance, or whose hormone dosages cannot be lowered to maintenance levels.

Adult-onset still\'s disease is a rare condition that is generally treated by glucocorticoids. Importantly, due to the limited established treatments, glucocorticoid-refractory cases are particularly difficult to treat. Between December 2009 and August 2022, nine patients with adult-onset Still\'s disease were treated with tocilizumab (tocilizumab group). The therapeutic efficacy and safety of tocilizumab initiation in the acute phase were evaluated in cases of initial onset and recurrence. We also compared the efficacy of tocilizumab with that of methotrexate (methotrexate group, n = 13), which has been the drug of choice for adjunctive therapy. Tocilizumab demonstrated the expected efficacy in all four patients who received it at relapse and in three of the five patients who received it at the initial onset. However, two patients developed macrophage activation syndrome following treatment. A comparison of treatment effects between the methotrexate and tocilizumab groups revealed that the ferritin and C-reactive protein levels, severity score, and glucocorticoid doses decreased over time in both groups; nonetheless, the tocilizumab group experienced a more stable effect. Tocilizumab is undoubtedly a valuable treatment option for adult-onset Still\'s disease, especially when administered at relapse. This suggests that it shows both high safety and good efficacy. Nevertheless, a larger sample size is required to validate the efficacy and safety of tocilizumab compared with those of the existing alternatives. Key Points • We examined the significance of TCZ in terms of therapeutic efficacy, reduction in glucocorticoid usage, and safety in patients with AOSD. • We compared the therapeutic efficacy of TCZ with that of MTX, which is often used to treat glucocorticoid-resistant AOSD. • TCZ is undoubtedly a valuable treatment option for AOSD, especially when administered at relapse, suggesting both high safety and good efficacy.

Tocilizumab has demonstrated optimal efficacy and safety in patients with rheumatoid arthritis (RA) from clinical trials. However, the risk of hepatitis B virus reactivation (HBVr) in these patients remains uncertain because patients with underlying HBV have been excluded in phase III studies.
Systematical reviews were conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to 21 February 2023. Random-effects meta-analysis was performed to calculate the pooled incidence of HBV reactivation.
We included 0 clinical trials and 11 observational studies with a total of 25 HBsAg+ and 322 HBsAg-/anti-HBc+ RA patients. Among the HBsAg+ patients without antiviral prophylaxis, the pooled rate was 69.4% (95% CI, 32.9-91.3), with a median time of 4 months (range, 1-8 months) from tocilizumab initiated. Half of these patients with HBVr experienced hepatitis flare-up but no deaths. HBVr was eliminated with prophylaxis in this population. Among HBsAg-/anti-HBc+ patients, the pooled incidence of reactivation was 3.3% (95% CI, 1.6-6.7), with a median time of 10 months (range, 2-43 months) from tocilizumab initiated. HBVr was not associated with hepatitis flare-up and death. HBsAg-/anti-HBc+ patients without anti-HBs antibodies had a significantly higher risk of HBVr (Odds ratio, 12.20; 95% CI, 1.16-128.06).
This systematic review indicated that the risk of HBVr in RA patients with anti-HBs-, HBsAg+, or HBsAg-/anti-HBc+ cannot be ignored but may be avoided. Clinicians should consider implementing appropriate antiviral prophylaxis and monitoring policies for RA patients to avoid unnecessary hepatic side effects from tocilizumab treatment.

BACKGROUND: Mevalonate kinase deficiency (MKD) and TNF receptor-associated periodic syndrome (TRAPS) are categorized as systemic autoinflammatory diseases (SAIDs), which are rare diseases characterized by early onset, severe conditions, and challenging diagnosis and treatment. Although different SAIDs have varying standard treatments, some SAIDs are poorly controlled after routine treatment, seriously affecting the growth and development of children and their quality of life. This study aims to provide more treatment strategies for SAIDs.
METHODS: We present two Chinese patients with MKD and TRAPS who were resistant to TNF- (tumor necrosis factor-) α blockade. After using etanercept, baricitinib, and glucocorticoid, patients with MKD and TRAPS still had periodic fever and rash. Due to the unavailability of IL-1 antagonists in the Chinese Mainland, we started administering intravenous tocilizumab (TCZ) at a dosage of 240 mg every three weeks. They had not experienced fever or rash after receiving one or two doses of TCZ. Before treatment with TCZ in the MKD patient, white blood cell (WBC) count, and TNF-α level were normal, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) increased significantly, and IL-6 increased slightly. After treatment with TCZ, ESR and CRP levels returned to normal; however, IL-6 increased occasionally. In the TRAPS patient, ESR, CRP, WBC, IL-6, and TNF-α levels were increased significantly. After TCZ treatment, ESR, CRP, WBC, IL-6, and TNF-α levels returned to normal. The two patients were treated with TCZ for more than six months and achieved clinical and serological remission. Furthermore, they had no adverse reactions after injection of TCZ.
CONCLUSIONS: In the absence of IL-1 antagonists in mainland China, tocilizumab emerges as an alternative drug in SAIDs that are resistant to TNF-α blockade.

Giant cell arteritis (GCA) is a chronic vasculitis that primarily affects the elderly, and can cause visual impairment, requiring prompt diagnosis and treatment. The global impact of the coronavirus disease 2019 (COVID-19) pandemic has been substantial. Although vaccination programs have been a key defense strategy, concerns have arisen regarding post-vaccination immune-mediated disorders and related risks. We present a case of GCA after COVID-19 vaccination with 2 years of follow-up. A 69-year-old woman experienced fever, headaches, and local muscle pain two days after receiving the COVID-19 vaccine. Elevated inflammatory markers were observed, and positron emission tomography (PET) revealed abnormal uptake in the major arteries, including the aorta and subclavian and iliac arteries. Temporal artery biopsy confirmed the diagnosis of GCA. Treatment consisted of pulse therapy with methylprednisolone, followed by prednisolone (PSL) and tocilizumab. Immediately after the initiation of treatment, the fever and headaches disappeared, and the inflammation markers normalized. The PSL dosage was gradually reduced, and one year later, a PET scan showed that the inflammation had resolved. After two years, the PSL dosage was reduced to 3 mg. Fourteen reported cases of GCA after COVID-19 vaccination was reviewed to reveal a diverse clinical picture and treatment response. The time from onset of symptoms to GCA diagnosis varied from two weeks to four months, highlighting the challenge of early detection. The effectiveness of treatment varied, but was generally effective similarly to that of conventional GCA. This report emphasizes the need for clinical vigilance and encourages further data collection in post-vaccination GCA cases.