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

Abstract

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.

Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients

“…Interestingly, it was also reported that withdrawal of hydrocortisone treatment results in an inflammatory rebound phenomenon in septic shock patients [14]. Like corticosteroids, tocilizumab treatment also reduced CRP levels in patients with rheumatoid arthritis and in those suffering from giant cell arteritis [15]. Also in COVID-19 patients, reduction in PCT and CRP levels was observed in patients treated with tocilizumab [16].…”

“…No differences in patient characteristics were observed between the secondary infection and nosecondary infection groups for the D−T−, D+T− and D+T+ groups (Table 2). In patients who developed a secondary infection, a positive culture was obtained on median [IQR] day 14 [11][12][13][14][15][16][17][18][19] following ICU admission, which was designated day 0 for the following analyses.…”

“…3d). When comparing the early and late secondary infection groups (development of secondary infection at 1 [− 1-2] and 12 [9][10][11][12][13][14][15][16] days after cessation of DEXA, respectively), the late infection group displayed a more pronounced increase in levels of both PCT and CRP following alignment day, with significantly higher levels of PCT on days 0 and 2 (Additional file 2: Fig. S2).…”

Case Report: Lessons Learned From Subsequent Autologous and Allogeneic Hematopoietic Stem Cell Transplantations in a Pediatric Patient With Relapsing Polychondritis

“…This relapse was characterized by a return of clinical symptoms (costochrondral pain, loss of appetite) and increased activity on an F-18-FDG PET scan. CRP level was probably not elevated at this time due to the masking effect of tocilizumab ( 10 ). After an unsuccessful attempt with abatacept, we concluded that for this patient with steroid-dependent relapsing polychondritis with severe steroid toxicity there were no other treatment options left, except for alloHSCT.…”

Preserved C-reactive protein responses to blood stream infections following tocilizumab treatment for COVID-19

“…One consequence of tocilizumab-mediated inhibition of the IL-6 signalling pathway is that routinely measured CRP concentrations are decreased [6]. In inflammatory arthritides, tocilizumab doses are administered every 2-4 weeks, resulting in variable attenuation of CRP responses to bacterial infection [7][8][9]. In COVID-19, single doses of tocilizumab are used [4,5], making the extent and duration of IL-6 signalling suppression less defined [10].…”