Candidiasis in patients treated with interleukin-17 inhibitors.

Sir,

Interleukin-17 (IL-17) is a cytokine produced by immune cells whose overproduction is associated with the abnormal inflammation, implicated in diseases such as psoriasis (Pso), psoriatic arthritis (PsA), rheumatoid arthritis, and ankylosing spondylitis.[1] Therefore, several monoclonal antibodies directed against this cytokine or its receptors have been developed and have shown their efficacy in clinical trials.[23]

IL-17-mediated immunity is a fundamental mechanism to protect the mucous membranes and skin from fungal infections. Hence, patients receiving anti-IL 17 antibodies may have a higher risk of these infections.[4]

Saunte et al. reviewed data from clinical trials concerning the risk of candidiasis for patients with Pso and PsA treated with anti-IL 17 antibodies.[2] The incidence of candidiasis reported was 1.7%, 3.3%, and 4.0% for secukinumab, ixekizumab, and brodalumab, respectively, versus 0.3%, 0.8%, and 2.3% of patients assigned to the control groups; placebo, etanercept, and ustekinumab, respectively. The authors concluded that candidiasis incidence was slightly increased for patients undertreatment with IL-17-targeted therapies. Furthermore, the authors recommended monitoring these patients during treatment for fungal infection.[2]

There are few studies of candidiasis in real-life patients treated with IL-17 inhibitors, suggesting that a complete assessment of the risk of infection from Candida spp is deemed necessary in this group of patients.[5]

To evaluate the incidence of candidiasis in real-life adult patients treated with IL-17 inhibitors, we conducted a retrospective observational study of patients treated with secukinumab and ixekizumab in a third-level hospital from December 2015 to December 2018.

The variables collected were demographics (age, sex), IL-17 inhibitor indication, treatment duration, time on treatment before developing candidiasis, and whether these patients presented potential risk factors to develop candidiasis. Obesity, type 2 diabetes mellitus, and age above 65 years were considered risk factors to develop candidiasis. The diagnosis of candidiasis was based on physicians' reports in electronic clinical charts.

Candidiasis incidence was measured after 52 weeks of treatment with anti-IL-17 therapy. For those cases where the treatment was interrupted before these 52 weeks, candidiasis incidence was measured on the actual treatment period. This methodology allowed us to compare our results to pivotal clinical trials.

All IL-17 inhibitors were administered according to the standard clinical practice. Table 1 shows patients' characteristics.

Table 1

Patients’ characteristics

Variables	Secukinumab	Ixekizumab
Demographics
Number of patients	140	45
Male/female	78/62	34/11
Mean age (years)	49 (19-85)	48 (19-73)
Diagnosis (%)
Pso	74 (52.86)	33 (73.33)
PsA	66 (47.14)	12 (26.6)
Candidiasis risk factors (%)
Obesity	47 (33.81)	2 (5)
DM2	13 (9.35)	3 (7)
Older 65 years (%)	19 (13.67)	5 (11)
Previous biologic therapy (%)	69 (49.29)	33 (73.33)
Mean treatment duration (weeks)	74.64 (4-194.71)	42.86 (7.86-20.86)

Pso=Psoriasis, PsA=Psoriatic arthritis, DM2=Type 2 diabetes mellitus

Among the 140 patients treated with secukinumab, four patients (2.86%) developed candidiasis. One of them developed two different episodes of candidiasis after 16 weeks (vulvovaginal) and 23 weeks (cutaneous) after starting secukinumab treatment. The rest of the patients developed candidiasis 16 weeks (cutaneous), 21 weeks (infection site not specified), and 32 weeks (oral) after starting secukinumab treatment. One of them presented risk factors for candidiasis.

Of the 45 patients treated with ixekizumab, three patients (6.6%) developed oral candidiasis, respectively, after 29, 25, and 43 weeks after the start of ixekizumab treatment. Two of the patients showed risk factors to develop candidiasis: the first was 73 years old, diabetic, and obese, and the other was 69 years old.

Patients who developed candidiasis were successfully managed with conventional antifungal treatment. Therefore, no discontinuations of IL-17 inhibitors treatment were necessary.

When comparing with Saunte et al. review, the incidence of candida infection in our population sample was increased, 2.68% versus 1.7% for secukinumab and 6.6% versus 3.3% for ixekizumab. Our study suggests that the incidence of candida infection in real-life patients could be even higher than the reported on clinical trials.

Further investigations are expected to set up the rate of candidiasis on patients treated with IL-17-targeted therapies. Patients going through such treatments ought to be checked for fungal infection and treated accordingly.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.