Secukinumab effectiveness has been demonstrated in both psoriasis (PsO) and psoriatic arthritis (PsA). However, it is unknown whether arthritis, compared to PsO alone, may represent a risk factor for withdrawal. Our aim was to identify predictors of secukinumab survival, including the presence of arthritis, in PsO and PsA.
Consecutive PsO and PsA patients initiating secukinumab were enrolled and followed-up every 6 months, up to 24-months or discontinuation. Medical history, disease activity indices and Body Mass Index (BMI) were collected. Kaplan-Meier curves and log-rank test were used to analyze differences in drug survival according to sex, BMI, biological therapy line in the whole population (psoriatic disease) and separately for PsO/PsA. A multivariable Cox-regression model was built to assess whether presence of arthritis (main independent variable) may influence drug survival by having time-to-secukinumb-discontinuation as outcome. Results were expressed as Hazard Ratio (HR) and 95% Confidence Interval (95%CI).
Sixty-two PsO and 90 PsA patients were enrolled (Table). Retention rate was 77% and 59% at 12- and 24-months. In the whole population, naïve patients displayed higher drug survival (log-rank=4.06; p=0.04); in PsA, obese patients were more likely to discontinue secukinumab (log-rank=5.25; p=0.021). The multivariable Cox-regression showed that arthritis was independently associated with a higher risk of secukinumab discontinuation (HR 2.43; 95%CI:1.06-5.55, p=0.035) after adjusting for age, sex, gender, BMI, therapy line and PsO severity at baseline.
Our data confirmed a good response to secukinumab in both PsO and PsA patients. However, presence of arthritis might affect drug survival.
Th17 and Tfh cells, sustain tissue inflammation and autoantibody production respectively in rheumatoid arthritis (RA). Tfh cells co-expressing Th17 markers (CXCR5+Th17), incorporate both pathogenic roles and are amplified in RA. We have previously shown that secukinumab, an anti-IL-17A biologic, decreases nuclear antigen-specific autoantibodies, plasmablasts and Tfh cells in patients with psoriatic disease (PSD). Our aim was to explore whether these cells can serve as predictive biomarkers of secukinumab-induced remission in PSD.
PBMCs were isolated from 12 psoriasis and 8 psoriatic arthritis (PsA) patients at baseline and 6-months following secukinumab administration. Disease activity and response to biological treatment was assessed using PASI and DAS28-CRP criteria respectively. Tfh cells, CXCR5+Th17 cells and plasmablasts were analyzed flow cytometrically using fluorochrome-conjugated monoclonal antibodies against conventional cell surface markers.
8 out of 12 psoriasis and 4 out of 8 PsA patients were classified as complete responders (CRs). In the CR group, the frequency of CXCR5+Th17 cells (gated as CCR6+ cells within CXCR5+CD4+ cells), was significantly reduced at 6 months compared to baseline (p<0.01). In contrast, there was no significant difference between baseline and 6-month levels in the non-responder group (NR). The percentages of CXCR5+Th17 cells at baseline positively correlated with PASI and DAS28-CRP scores. Reduced percentages of CXCR5+Th17, Tfh cells and plasmablasts at 6 months (as compared to baseline levels) were associated with low PASI scores in psoriasis CRs.
High levels of CXCR5+Th17, Tfh cells and plasmablasts can be indicative of an impartial clinical response to secukinumab in psoriatic disease.