Risk of neutropenia in psoriasis patients prescribed anti-IL-23 antibody in comparison with anti-IL-17 antibody or adalimumab based on real-world data from the MID-NET^® in Japan

Figures & data

Figure 1. Flow chart for patient selection.

Table 1. Summary of patient background at the baseline.

	Anti-IL-23 antibodies^a	Anti-IL-17 antibodies^a (primary control)	Adalimumab^a (secondary control)	Apremilast^a (secondary control)
N patients	287	189	293	540
	N (%)	N (%)	N (%)	N (%)
Age, mean (SD)	54.1 (15.2)	56.1 (15.0)	51.5 (13.2)	59.7 (15.7)
Sex
Male	175 (61.0)	110 (58.2)	189 (64.5)	327 (60.6)
Baseline neutrophil count
≥ 2,000/μL	220 (76.7)	144 (76.2)	233 (79.5)	234 (43.3)
1,500/μL ≤ < 2,000/μL	< 10 (< 3.5)	< 10 (< 5.3)	< 10 (< 3.4)	< 10 (< 1.9)
Unknown	< 66 (< 23.0)	< 44 (< 23.3)	< 59 (< 20.1)	< 305 (< 56.5)
Pre-prescription of infliximab or certolizumab pegol	56 (19.5)	34 (18.0)	46 (15.7)	< 10 (< 1.9)
Psoriasis-related diagnosis (ICD10 code)
Psoriasis vulgaris (L400)	241 (84.0)	132 (69.8)	195 (66.6)	474 (87.8)
Generalized pustular psoriasis (L401)	19 (6.6)	24 (12.7)	15 (5.1)	12 (2.2)
Guttate psoriasis (L404)	0 (0)	< 10 (< 5.3)	< 10 (< 3.4)	< 10 (< 1.9)
Psoriasis arthropathica (L405)	57 (19.9)	85 (45.0)	114 (38.9)	69 (12.8)
Other psoriasis (L408)	< 10 (< 3.5)	< 10 (< 5.3)	< 10 (< 3.4)	< 10 (< 1.9)
Psoriasis, unspecified (L409)	32 (11.1)	27 (14.3)	64 (21.8)	67 (12.4)
Concomitant medications
Antiviral drugs	< 10 (< 3.5)	< 10 (< 5.3)	< 10 (< 3.4)	< 10 (< 1.9)
Drugs with very high risk for developing neutropenia^b	14 (4.9)	12 (6.3)	42 (14.3)	18 (3.3)
Drugs with high risk for developing neutropenia^c	75 (26.1)	60 (31.7)	134 (45.7)	116 (21.5)
Corticosteroids	205 (71.4)	141 (74.6)	202 (68.9)	354 (65.6)
Lithium carbonate	< 10 (< 3.5)	< 10 (< 5.3)	0 (0)	< 10 (< 1.9)
Complications
Renal impairment
Severe (eGFR < 30)	11 (3.8)	< 10 (< 5.3)	< 10 (< 3.4)	14 (2.6)
Non-severe (eGFR ≥ 30)	259 (90.2)	168 (88.9)	268 (91.5)	331 (61.3)
Unknown	17 (5.9)	< 20 (< 10.6)	< 24 (< 8.2)	195 (36.1)
Autoimmune disease other than psoriasis	147 (51.2)	144 (76.2)	201 (68.6)	177 (32.8)
Vitamin B12 or folic acid deficiency	23 (8.0)	40 (21.2)	76 (25.9)	31 (5.7)
Aplastic anemia	< 10 (< 3.5)	< 10 (< 5.3)	0 (0)	0 (0)
Cirrhosis or hypersplenism	21 (7.3)	16 (8.5)	13 (4.4)	17 (3.1)
Pheochromocytoma or Cushing’s syndrome	11 (3.8)	< 10 (< 5.3)	< 10 (< 3.4)	< 10 (< 1.9)

^a : When the number of patients was <10, an aggregated value was presented based on the MID-NET^® publication rule, so that a specific number could not be identified.

^b : Drugs with a very high risk of developing neutropenia: antithyroid drugs (thiamazole or propylthiouracil), phenothiazine antipsychotics, ticlopidine, salazosulfapyridine, or a combination of sulfamethoxazole and trimethoprim.

^c : High-risk drugs for developing neutropenia: H₂ receptor antagonists, interferon preparations, allopurinol, ritodrine, aprindine, valsartan, carbamazepine, glycopeptide antibiotics, carbapenem antibiotics, levofloxacin, proton pump inhibitors, edaravone, Chinese medicine (hangekobokuto), diaphenylsulfone, and methotrexate.

Figure 2. Comparison of neutropenia in anti-IL-23 antibody group with anti-IL-17 antibody, adalimumab, and apremilast groups.

CI: confidence interval, cHR: crude hazard ratio, aHR: adjusted hazard ratio, –: not applicable.

1: When the number of patients was <10, an aggregated value was presented based on the MID-NET^® publication rule, so that a specific number could not be identified.

2: aHR, weighted by the inverse of the propensity score, which was estimated using a logistic regression model including covariates (see Supplementary Table S3 for the list of covariates considered in this study).

Table 2. Summary of results from the sensitivity analysis (anti-IL-23 antibody vs. anti-IL-17 antibody, adalimumab, or apremilast).

		vs. anti-IL-17 antibody (primary control)	vs. adalimumab (secondary control)	vs. apremilast (secondary control)
Outcome	Condition for analysis*	aHR (95% CI)	aHR (95% CI)	aHR (95% CI)
Grade 2 neutropenia (neutrophil count < 1,500/μL)	Primary analysis	0.83 (0.27–2.51)	0.76 (0.28–2.06)	3.88 (0.62–24.48)
	Sensitivity analysis (1) limiting the study population to patients with normal neutrophil counts (2,000/μL to 7,500/μL) in the period from 90 days before t0 to the day before t0	0.41 (0.09–1.84)	0.49 (0.12–1.99)	0.48 (0.03–6.67)
	Sensitivity analysis (2) doubling the periods of gap and grace	0.86 (0.31–2.39)	0.76 (0.29–1.96)	4.16 (0.71–24.47)
	Sensitivity analysis (3) excluding infliximab, certolizumab pegol, anti-cancer drugs, and clozapine from the list of drugs considered for terminating the follow-up period	0.83 (0.27–2.52)	0.78 (0.28–2.12)	1.90 (0.34–10.63)
Grade 3 neutropenia (neutrophil count < 1,000/μL)	Primary analysis	0.40 (0.02–7.60)	Incalculable	0.43 (0.02–11.63)
	Sensitivity analysis (1) limiting the study population to patients with normal neutrophil counts (2,000/μL to 7,500/μL) in the period from 90 days before t0 to the day before t0	0.34 (0.02–6.03)	Incalculable	0.33 (0.01–9.07)
	Sensitivity analysis (2) doubling the periods of gap and grace	0.31 (0.02–3.88)	Incalculable	0.52 (0.02–11.57)
	Sensitivity analysis (3) excluding infliximab, certolizumab pegol, anti-cancer drugs, and clozapine from the list of drugs considered for terminating the follow-up period.	0.40 (0.02–7.64)	Incalculable	0.17 (0.01–2.53)

CI: confidence interval, aHR: adjusted hazard ratio.

* : see ‘Methods’ for more details.

Data availability statement

The dataset generated in the study is not publicly available due to the terms of use for MID-NET^® to which we adhered when conducting this study; the accessibility of the dataset used for this analysis is restricted to specific authors including the corresponding author in a predetermined secure environment. No outside researchers are allowed to access the dataset.