Association Between Decreased Neutrophil Counts and Serious Infection With TCZ in RA

Patients with rheumatoid arthritis receiving intravenous tocilizumab (TCZ) had greater grade 1/2 and grade 3/4 neutrophil counts compared with a placebo-controlled group but decreased neutrophils during treatment and a lower risk for serious infection in the group within 30 days, according to recent research published in Rheumatology.¹

In a pooled analysis, Robert J. Moots, MD, PhD, from the Department of Musculoskeletal Biology at the University of Liverpool, and colleagues used data from phase 3/4 clinical trials, pharmacology studies, and long-term extensions to identify 4171 patients (16,204.8 patient-years) with rheumatoid arthritis who were either taking intravenous TCZ or were in a control group receiving a placebo.

The researchers analyzed the placebo-controlled portions of trials and long-term extensions and identified 1454 patients who received placebo plus disease-modifying antirheumatic drugs (DMARDs) and 2644 patients who received TCZ ± DMARDS. The TCZ group was further divided by dosage rate into patients receiving 4 mg/kg TCZ + methotrexate, 8 mg/kg TCZ ± DMARDs, and 10 mg/kg TCZ.

“We found that in placebo-controlled parts of trials, more TCZ-treated than placebo-treated patients had grade 1/2 or 3/4 neutrophil counts, and when neutrophil counts decreased, they did so for up to 6 weeks from baseline before stabilizing,” Dr Moots told Rheumatology Advisor in an interview.

“Importantly, any decreases in neutrophil counts in patients taking TCZ did not appear to be associated with serious infections and were normalized by current risk-mitigation guidelines.”

Specifically, 28.2% of patients in the TCZ group had grade 1/2 neutrophil counts compared with 3.1% of patients in the placebo group; similarly, 8.9% of patients receiving TCZ had grade 3/4 neutrophil counts compared with 0.2% of patients in the placebo group, according to the abstract. There was a mean change in neutrophil counts of −2.17 × 10⁹/L from baseline through 6 weeks, with no change in neutrophils seen after 6 weeks. Dr Moots and colleagues also found grade 3/4 neutrophil counts were associated with female sex (odds ratio, 2.55; 95% confidence interval [CI], 1.40-4.66) and a baseline neutrophil count lower than 2 × 10⁹/L (odds ratio, 19.02; 95% CI, 6.76-53.52).

Regarding risk for infection, there were similar rates of serious infection among patients with normal neutrophil counts (4.66; 95% CI, 4.31-5.03), grade 1/2 neutrophil counts (2.48; 95% CI, 1.79-3.34), and grade 3/4 neutrophil counts (2.77; 95% CI, 0.34-10.01) within 30 days.

Summary & Clinical Applicability

The researchers noted that because neutrophil decreases in patients taking TCZ do not increase the risk for serious infection, TCZ is an effective risk-mitigation strategy.

“Neutrophil decreases typically occur on one visit or two consecutive visits,” Dr Moots and colleagues wrote. “Although infections may develop in patients during TCZ treatment, no temporal relationship between decreased neutrophil count and serious infection has been observed to date.”

Disclosures 

Dr Moots has given scientific advice, received grant support, or is a paid speaker for Bristol-Myers Squibb (BMS), Chugai, Celgene, Merck Sharp & Dohme (MSD), Novartis, Pfizer, and UCB Pharma. Donaldson and Dimonaco are paid employees of Roche Products Ltd. Oster received support from and is a paid consultant for Roche, Chugai, MSD, AbbVie, Pfizer, Novartis, Lilly, and BMS. Genovese has received grants from Roche, Sanofi, and GlaxoSmithKline (GSK) and has held consultancies with Roche, Sanofi, GSK, Pharma, and Bird Rock Bio. van Vollenhoven received grant support from AbbVie, Amgen, BMS, GSK, Pfizer, Roche, and UCB and received consulting fees and honoraria from AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, and Vertex. Porter-Brown is a paid employee of F. Hoffmann-La Roche Ltd. Rubbert-Roth received consulting and presentation honoraria from Roche and Chugai. Sebba is on the speaker’s bureau for Genentech, Lilly and Company, and Novartis, and has received compensation for clinical research from Genentech, Lilly, Jansen and Jansen, Pfizer, Sandoz, and Novartis. Rigby has received consulting honoraria and received grant support from Roche for clinical trials.

Reference

Moots RJ, Sebba A, Rigby W, et al. Effect of tocilizumab on neutrophils in adult patients with rheumatoid arthritis: pooled analysis of data from phase 3 and 4 clinical trials [published online December 24, 2016]. Rheumatology (Oxford). doi: 10.1093/rheumatology/kew370

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