Table 4: Proportions of patients who experienced neutropenia during RA treatment in clinical .

% of ≤6 months>6 monthsClinical sequelae
Grade 3 or 4Grade 3 or 4

Conventional synthetic

Methotrexate0.4% [60]N/AN/A

LeflunomideGrade 4: 0% [61]N/AN/A

SulfasalazineN/A0% [63]N/A

Biologic

AdalimumabGrade 2 or 3: <1.0% [62]≤1.0% [62]N/A

InfliximabN/AGrade 2, 3, or 4: 1.7%8.8% [93]N/A

EtanerceptN/A0% [63]N/A

Golimumab≥1 abnormal value: 2.3%N/AN/A

TocilizumabGrade 3: 4.8% [27] 
Grade 4: <1.0% [27]
N/AOne patient experienced a serious infection of empyema temporally associated with grade 3 neutropenia. None of the patients with grade 4 neutropenia experienced serious infection within 30 days of observed neutropenia [27]

RituximabLON: 4.6%6% [64, 65]N/ALON was defined as an ANC < 1.0 × 109/L occurring 4 weeks after the last rituximab infusion.
Most cases resolved spontaneously or following administration of G-CSF or GM-CSF. Febrile neutropenia and neutropenia-related infections requiring hospitalization have been observed

AbataceptN/AN/AN/A

Anakinra0.4% [94]0.5% [90]While neutropenic, 1 patient developed cellulitis.
In most cases, grade 3 or 4 toxic events were sporadic and were not associated with progressive decreases nor were indicative of drug-related impairment [90]

Targeted small-molecule DMARDs

Tofacitinib<1% [92] 
Grade 2 or 3: 0.9%3.1% [60, 91, 92] 
Grade 4: 0% [91]
Grade 2 or 3: 1.3% [92]N/A

ANC, absolute neutrophil count; DMARD, disease-modifying antirheumatic drug; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; LON, late-onset neutropenia; N/A, not available; RA, rheumatoid arthritis; TCZ, tocilizumab. grades were defined as follows: grade 2, ≥1000 to <1500 cells/mm3; grade 3, ≥500 to <1000 cells/mm3; grade 4, <500 cells/mm3. are the proportions of patients experiencing grade 3 or 4 ANCs except where noted. were not available for hydroxychloroquine/chloroquine or certolizumab. a cohort of patients with polyarticular juvenile idiopathic arthritis who received infliximab plus methotrexate. medical letter (personal communication), data on file.