Five-year safety of tildrakizumab in patients with moderate-to-severe psoriasis from two phase 3 trials (reSURFACE 1 and reSURFACE 2): number needed to harm for occurrence of adverse events of special interest

Figures & data

Table 1. Baseline characteristics of the safety population.

	Tildrakizumab 100 mg (N = 872)	Tildrakizumab 200 mg (N = 928)
Male, n (%)	626 (71.8)	659 (71.0)
Age (years), mean (SD)	45.7 (13.3)	45.9 (13.3)
Weight (kg), mean (SD)	89.1 (23.2)	88.6 (22.8)
BMI (kg/m^2), mean (SD)	29.8 (7.1)	29.8 (7.4)
BSA (%), mean (SD)	31.8 (17.8)	31.2 (17.3)
PASI score, mean (SD)	20.0 (7.7)	20.2 (7.9)
PGA category, n (%)
≤3	580 (66.7)	613 (66.5)
≥4	289 (33.3)	309 (33.5)
Psoriatic arthritis (yes), n (%)	136 (15.6)	143 (15.4)
Previously treated with biologics, n (%)	142 (16.3)	160 (17.2)

BMI: body mass index; BSA: body surface area; PASI: Psoriasis Area Severity Index; PGA: Physician’s Global Assessment; SD: standard deviation.

Table 2. Exposure-adjusted incidence rates of adverse events through weeks 256/244 in reSURFACE 1 and reSURFACE 2 studies.

Preferred term	Tildrakizumab 100 mg (N = 872)	Tildrakizumab 200 mg (N = 928)
Total follow-up, PYs	2688.4	2753.5
Any TEAE	5232 (194.6 [189.2–200.0])	5577 (202.5 [197.1–208.0])
Drug-related TEAEs	793 (29.50 [27.40–31.59])	1040 (37.77 [35.43–40.11])
Any SAE	249 (9.26 [8.09–10.44])	245 (8.90 [7.76–10.03])
Drug-related SAEs	24 (0.89 [0.53–1.26])	16 (0.58 [0.29–0.87])
AEs leading to death	11 (0.41 [0.16–0.66])	5 (0.18 [0.02–0.34])
TEAEs leading to discontinuation	52 (1.93 [1.40–2.47])	40 (1.45 [0.99–1.91])
Drug-related AEs leading to discontinuation	19 (0.71 [0.38–1.03])	10 (0.36 [0.13–0.59])
SAEs leading to discontinuation	31 (1.15 [0.74–1.57])	23 (0.84 [0.49–1.18])
Drug-related SAEs leading to discontinuation	9 (0.33 [0.11–0.56])	5 (0.18 [0.02–0.34])

AE: adverse event; PYs: patient-years; SAE: serious adverse event; TEAE: treatment-emergent adverse event. Data shown as n (number of events per 100 patient-years of exposure [95% confidence interval]).

Table 3. Exposure-adjusted incidence rates of adverse events occurring in ≥5% of patients in one or more treatment groups through weeks 256/244 in reSURFACE 1 and reSURFACE 2 studies.

Preferred term	Tildrakizumab 100 mg (N = 872)	Tildrakizumab 200 mg (N = 928)
Total follow-up, PYs	2688.4	2753.5
Arthralgia	104 (3.87 [3.11–4.63])	116 (4.21 [3.43–5.00])
Back pain	72 (2.68 [2.05–3.31])	88 (3.20 [2.51–3.88])
Bronchitis	62 (2.31 [1.72–2.89])	82 (2.98 [2.32–3.64])
Cough	67 (2.49 [1.88–3.10])	80 (2.91 [2.26–3.56])
Diarrhea	77 (2.86 [2.21–3.52])	71 (2.58 [1.97–3.19])
Gastroenteritis	54 (2.01 [1.46–2.56])	61 (2.22 [1.65–2.78])
Headache	99 (3.68 [2.94–4.42])	105 (3.81 [3.07–4.56])
Hypertension	92 (3.42 [2.71–4.14])	108 (3.92 [3.17–4.68])
Influenza	79 (2.94 [2.28–3.60])	104 (3.78 [3.04–4.52])
Injection site erythema	11 (0.41 [0.16–0.66])	35 (1.27 [0.84–1.70])
Injection site reaction	5 (0.19 [0.02–0.35])	9 (0.33 [0.11–0.54])
Nasopharyngitis	644 (23.95 [22.07–25.84])	643 (23.35 [21.51–25.19])
Nausea	29 (1.08 [0.68–1.48])	42 (1.53 [1.05–2.00])
Oropharyngeal pain	40 (1.49 [1.02–1.96])	47 (1.71 [1.21–2.20])
Pruritus	37 (1.38 [0.92–1.83])	39 (1.42 [0.96–1.87])
Psoriasis	31 (1.15 [0.74–1.57])	37 (1.34 [0.90–1.79])
Sinusitis	74 (2.75 [2.11–3.39])	67 (2.43 [1.84–3.03])
Upper respiratory tract infection	179 (6.66 [5.66–7.65])	213 (7.74 [6.68–8.80])
Urinary tract infection	69 (2.57 [1.95–3.18])	67 (2.43 [1.84–3.03])

PYs: patient-years. Data shown as n (number of events per 100 patient-years of exposure [95% confidence interval]).

Table 4. Exposure-adjusted incidence rates of adverse events of special interest through weeks 256/244 in reSURFACE 1 and reSURFACE 2 studies.

Preferred term	Tildrakizumab 100 mg (N = 872)	Tildrakizumab 200 mg (N = 928)
Total follow-up, PYs	2688.4	2753.5
Severe infection	38 (1.41 [0.95–1.87])	48 (1.74 [1.24–2.25])
Malignancy excluding NMSC	21 (0.78 [0.44–1.12])	17 (0.62 [0.32–0.92])
NMSC	14 (0.52 [0.24–0.80])	16 (0.58 [0.29–0.87])
Melanoma	3 (0.11 [0.00–0.24])	3 (0.11 [0.00–0.23])
Confirmed extended MACE	15 (0.56 [0.27–0.85])	24 (0.87 [0.52–1.23])
Injection-site reaction^a	67 (2.49 [1.88–3.10])	86 (3.12 [2.45–3.80])
Drug-related hypersensitivity reaction	14 (0.52 [0.24–0.80])	5 (0.18 [0.02–0.34])

MACE: major adverse cardiovascular event; NMSC: non-melanoma skin cancer; PYs: patient-years. Data shown as n (number of events per 100 patient-years of exposure [95% confidence interval]). ^aNot recorded during the extension studies.

Table 5. Number needed to harm for occurrence of adverse events of special interest with tildrakizumab 100 mg and 200 mg corrected for the baseline risk in reference population with psoriasis.

			Tildrakizumab 100 mg (N = 872)			Tildrakizumab 200 mg (N = 928)
		Total follow-up, PYs	2688.4			2753.5
		Exposure-adjusted incidence rate^a in the PSOLAR [9,10]	Number of events	Exposure-adjusted incidence rate^a	NNH	Number of events	Exposure-adjusted incidence rate^a	NNH
AESI	Severe/Serious infection	0.0150^b	38	0.01413	−1149.4	48	0.01743	411.5
	Malignancy	0.0068^b	21	0.00781	990.1	17	0.00617	−1587.3
	Extended MACE/MACE	0.0059^b	15	0.00558	−3125.0	24	0.00872	354.6

AESI, adverse event of special interest; MACE, major adverse cardiovascular event; NNH, number needed to harm; PSOLAR, Psoriasis Longitudinal Assessment and Registry; PYs, patient-years. ^aNumber of events per patient-year of exposure. ^bTotal cumulative incidence rate. In reSURFACE trials, ‘severe infections’ were either those infections meeting the regulatory definition of a serious adverse event or those requiring intravenous antibiotics; non-melanoma skin cancer was excluded from ‘malignancies’; and ‘extended MACEs’ included non-fatal myocardial infarction, non-fatal stroke, unstable angina, coronary revascularization, resuscitated cardiac arrest, and cardiovascular deaths that were confirmed as ‘cardiovascular’ or ‘sudden’. In PSOLAR, ‘serious infections’ were either those requiring hospitalization or considered medically important; non-melanoma skin cancer was also excluded from ‘malignancies’; and ‘MACE’ comprised cardiovascular death, non-fatal cerebrovascular accident and non-fatal myocardial infarction.

Positive NNH values are marked in bold.

Gottlieb AB, Kalb RE, Langley RG, et al. Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies. J Drugs Dermatol. 2014;13(12):1441–1448.

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Gottlieb AB, Langholff W. Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies errata. J Drugs Dermatol. 2020;19(6):573–574.

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Data availability statement

The datasets generated or analyzed during this study are available from the corresponding author on reasonable request.