Prodromal signs and symptoms of serious infections with tocilizumab treatment for rheumatoid arthritis: Text mining of the Japanese postmarketing adverse event-reporting database

Atsumi, Tatsuya; Ando, Yumiko; Matsuda, Shinichi; Tomizawa, Shiho; Tanaka, Riwa; Takagi, Nobuhiro; Nakasone, Ayako

doi:10.1080/14397595.2017.1366007

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…Nevertheless, the 'frequent infection' hypothesis remains an alternative explanation for these findings, especially as immune dysregulation may occur in the years before diagnosis and increase infection risk. Pulmonary involvement, particularly interstitial lung disease, is a recognised concomitant of RA though it is believed to occur subsequent to joint involvement [23,24], sometimes being related to treatment [25], and is often asymptomatic in its early stages.…”

Section: Discussionmentioning

confidence: 99%

Influence of prior antibiotic use on risk of rheumatoid arthritis: case control study in general practice

et al. 2019

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Objectives To test the hypothesis that prior antibiotics influences the risk of developing RA. Methods A case–control study was conducted over 15 years using the UK’s Royal College of General Practitioners Research and Surveillance Centre database. The frequency and type of antibiotic prescription for patients who subsequently developed RA were compared with antibiotic prescriptions in a control group of patients who remained free of RA. Cases, defined as patients with a new diagnosis of RA made between 2006 and 2018, were matched with up to four RA-free controls on practice, age, gender and date of diagnosis. Exposure was measured by the number and type of prescriptions for antibiotics prior to the RA diagnosis or to the index date in controls. Results A total of 8482 patients with a new diagnosis of RA between 2006 and 2018 were compared with 22 661 controls. There was a higher likelihood of an RA diagnosis after antibiotic prescriptions within 1 year, 5 years and ever with a strong dose–response. Patients receiving >10 antibiotics in a 5 year period were more than twice as likely to receive an RA diagnosis as controls [adjusted odds ratio 2.65 (CI 2.40, 2.93)]. Conclusion Exposure to antibiotics prior to the diagnosis was a significant risk factor for RA. This could reflect an immunological response to a compromised microbiome. Alternatively, patients with pre-symptomatic or early undiagnosed RA may have been more likely to present to their general practitioner with infections due to an unrecognized effect of RA.

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Section: Discussionmentioning

confidence: 99%

Influence of prior antibiotic use on risk of rheumatoid arthritis: case control study in general practice

et al. 2019

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“…Overlooking early symptoms of infection such as cough, sputum, nasal discharge, or sore throat when receiving TCZ therapy in daily clinical practice is a problem. However, most patients experience the above-mentioned signs or symptoms of infection before developing a serious infection [76]. Since the symptoms of infection are relatively mild during TCZ therapy, patients may postpone hospitalization; however, the increasing severity of the infection can significantly harm the patients.…”

Section: Safety Of the Il-6 Inhibitor In Ramentioning

confidence: 99%

IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review

Ogata

Kato

Higa

et al. 2019

Modern Rheumatology

147

124

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Tocilizumab (TCZ) is an interleukin-6 (IL-6) inhibitor used for the treatment of rheumatoid arthritis (RA). It was developed in 2008, and its effectiveness is supported by evidence from all over the world based on its first decade of use. Although the overall efficacy and safety profiles of TCZ are similar to those of tumor necrosis factor (TNF) inhibitors, TCZ displays certain differences. The most notable advantage of TCZ is its usefulness as a monotherapy. Additionally, TCZ is favorable in the improvement of systemic inflammatory symptoms such as anemia and fatigue. The low immunogenicity of TCZ contributes favorably to long-term drug retention. Due to frequent relapse after TCZ cessation, TCZ use should be tapered beyond remission. During TCZ therapy, C-reactive protein (CRP) is unable to recognize disease activity and the severity of infection. The most common adverse events (AEs) are infection and abnormalities in laboratory findings including dyslipidemia, neutropenia, thrombocytopenia, and abnormality of liver enzymes. TCZ obscures the symptoms of infection. Therefore, stealth infections without obvious CRP elevation can sometimes cause severe damage to patients. Lower intestinal perforation is an uncommon but serious AE in TCZ therapy. Further clinical investigations will continue to refine the IL-6 inhibitory strategy.

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“…In a retrospective Japanese report that used text mining, 60.7% of patients had signs/symptoms 28 days before a severe infection was diagnosed. The most frequent signs/symptoms were for infections of the skin (swelling and pain) and respiratory system (cough and pyrexia) [46]. Among 68 patients who had normal CRP levels, body temperature, and white blood cell counts, 94% had signs or symptoms of infection.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature

Berman

Ben‐Ami

Berliner

et al. 2021

Life

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Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009–2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis.

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Prodromal signs and symptoms of serious infections with tocilizumab treatment for rheumatoid arthritis: Text mining of the Japanese postmarketing adverse event-reporting database

Cited by 8 publications

References 26 publications

Influence of prior antibiotic use on risk of rheumatoid arthritis: case control study in general practice

Influence of prior antibiotic use on risk of rheumatoid arthritis: case control study in general practice

IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review

The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature

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