Table 3.
Event rates and risk ratios of candidiasis in the population-based drug prescriptions registry (PHARMO).
| All patients (any indication) with IL-17 inhibitor therapy(N = 215)a(Exposure = 231.2 PY)(Treatment episodes = 246) | All patients (any indication) with TNF-α inhibitor therapy(N = 5,167)(Exposure = 12,212.7 PY)(Treatment episodes = 8,390) | Healthy controlsb(N = 33,051)(Years of follow-up in database = 380,212.2 PY) | |
|---|---|---|---|
| Candida infections incidence ratec | no. patients IR (95% CI)d |
no. patients IRRRe |
no. patientsIRRR |
| All Candida infections | 31 IR 13.4 |
706 IR 5.8 RR 2.4 |
15,257 IR 4.0 RR 3.4 |
| Candida infections event ratec | no. events ER (95% CI) |
no. events ER (95% CI) RR (95% CI) |
no. events ER (95% CI) RR (95% CI) |
| All Candida infections | 42 ER 20.96 (13.85-31.71) |
1205 ER 11.07 (10.10-12.14) RR 1.99 (1.27-3.11) p=0.003f |
22,799 ER 6.46 (6.28-6.64) RR 2.46 (1.46-4.16) p<0.001 |
| Cutaneous candidiasis | 24 ER 10.66 (6.67-17.05) |
652 ER 5.56 (5.16-6.11) RR 1.94 (1.11-3.42) p=0.02 |
12,929 ER 3.62 (3.52-3.72) RR 2.98 (1.74-5.12) p<0.001 |
| Oropharyngeal candidiasis | 5 ER 4.50 (1.27-16.02) |
65 ER 0.62 (0.43-0.90) RR 9.59 (1.70-53.94) p=0.01 |
703 ER 0.24 (0.21-0.28) RR 4.13 (0.56-30.52) p=0.17 |
| Onychomycosis | 1 ER 0.44 (0.06-3.13) |
46 ER 0.38 (0.28-0.51) RR 0.97 (0.14-6.78) p=0.98 |
902 ER 0.24 (0.22-0.25) RR 2.24 (0.31-15.99) p=0.42 |
| Vulvovaginal candidiasis Vulvovaginal candidiasis |
5 ER 2.23 (0.75-6.60) |
243 ER 2.31 (1.90-2.81) RR 0.90 (0.28-2.95) p=0.87 |
5,840 ER 1.53 (1.45-1.62) RR 1.44 (0.33-6.28) P=0.63 |
| All chronic Candida infectionsg | 35 ER 10.63 (5.79-19.52) |
272 ER 2.46 (2.10-2.88) RR 5.17 (3.13-8.51) p<0.001 |
4,377 ER 1.21 (1.12-1.26) RR 9.60 (4.96-18.58) p<0.001 |
| Cutaneous candidiasis | 21 ER 8.06 (4.61-14.11) |
160 ER 1.35 (1.14-1.60) RR 2.54 (1.20-5.41) p=0.02 |
2,917 ER 0.81 (0.77-0.84) RR 11.33 (4.15-30.94) p<0.001 |
| Oropharyngeal candidiasis | 4 ER 1.99 (0.60-6.60) |
12 ER 0.10 (0.06-0.18) RR 42.20 (12.26-145.29) p<0.001 |
106 ER 0.029 (0.02-0.04) RR 67.87 (9.57-481.11) p<0.001 |
| Onychomycosis | 0 N/A |
13 N/A |
214 N/A |
| Vulvovaginal candidiasis | 4 ER 0.83 (0.13-5.49) |
46 ER 0.44 (0.30-0.66) RR 1.63 (0.42-6.33) p=0.48 |
758 ER 0.20 (0.18-0.22) RR 12.94 (1.25-134.13) p=0.03 |
N indicates the number of patients in the PHARMO database. Exposure denotes the total amount of person-years (PY) of exposure. Individual drugs were anti-IL17, secukinumab and ixekizumab. Anti-TNFα, etanercept, adalimumab, and infliximab. Treatment episodes indicate the number of treatment episodes for all patients in the cohort, a patient can have more than one treatment episode with the same or with another biologic in the same cohort.
Patients without a calcipotriol/betamethasone prescription and without a biologic prescription during registration in PHARMO database.
Candida infections denote the sum of all single and chronic infections. Single infections are defined as ≥ 28 days between calculated end date and new prescription date for the same type of Candida infection. Chronic infections are defined as <10 days between calculated end date and new prescription date for the same type of Candida infection. For onychomycosis and cutaneous candidiasis prescription end dates could not be calculated. Events of cutaneous candidiasis were counted as separate events when there were ≥100 days between prescription dates, preventing standard 90 days’ prescription renewals to count as separate events. Events with <100 days between prescription dates were seen as chronic events. Separate events of onychomycosis were defined as ≥365 days between prescription dates, since these infections often require months of treatment and treatment is often non or not completely successful. Events with <365 days between prescription dates were seen as chronic events.
IR (95% CI) denotes the incidence rate per 100 patient years of exposure, ER (95% CI) denotes the event rate per 100 patient years of exposure and its 95% confidence interval. The raw analysis was used for IR and ER calculations.
RR (95% CI) denotes the risk ratio of IL-17 inhibitor therapy relative to TNF-α inhibitor therapy or relative to the outpatient pharmacy background population and its 95% confidence interval. The RR for the IR are the unadjusted estimates, the RR for the ER are the adjusted estimates derived from a mixed Poisson regression model.
P values were derived from a mixed Poisson regression model, p values are given in comparison to all patients (any indication) with IL-17 inhibitor therapy.
All chronic Candida infections denote the sum of all chronic Candida infections. Chronic infections are defined as <10 days between prescriptions for the same type of Candida infection.