Drug survival in patients with psoriasis is associated with the availability of biologic medications.

BACKGROUND: Drug survival rates in patients with psoriasis had been described extensively. Different survival rates of TNF-α inhibitors (TNFIs), ustekinumab and secukinumab were reported. OBJECTIVES: To investigate drug survival rates of TNFIs, ustekinumab and secukinumab, with particular emphasis on the difference between ustekinumab and secukinumab. METHODS: Survival analysis was performed in patients with moderate-to-severe psoriasis who received adalimumab, infliximab, etanercept, ustekinumab and secukinumab treatment in 2002-2018, using the Clalit Health Services database. Stratified analysis was performed according to biologic treatment lines. Multivariate analysis was performed adjusting for demographic variables, calendar year, metabolic syndrome, psoriatic arthritis, biologic treatment line, biologic naivety, co-administration of oral treatments and previous oral systemic treatment exposure. RESULTS: Among 1459 patients treated with 3070 biologic medication courses, ustekinumab had a significantly higher crude survival as compared with TNFIs and secukinumab. The mean drug survival of ustekinumab, adalimumab, etanercept, infliximab and secukinumab was 43.5 (CI: 39.7-47.2), 38.2 (CI: 34.8-41), 33.9 (CI: 30.8-37.1), 28.2 (CI: 22.5-33.8) and 17.1 (CI: 15.6-18.6) months, respectively, with significant statistical differences for all comparisons (P < 0.001). The differences between ustekinumab and secukinumab were not significant following adjustment to factors that included treatment line (hazard rate 1.16, CI: 0.93-1.43). CONCLUSION: Different drug survival rates between ustekinumab and secukinumab are determined by the treatment line and calendar year, reflecting the availability of biologic medications, and not only by the biologic attributes of each medication.

Cumulative exposure to biological therapy and risk of cancer in patients with psoriasis: a meta-analysis of Psonet studies from Israel, Italy, Spain, the U.K. and Republic of Ireland.

BACKGROUND: Cancer risk following long-term exposure to systemic immunomodulatory therapies in patients with psoriasis is possible. OBJECTIVES: To assess a dose-response relationship between cumulative length of exposure to biological therapy and risk of cancer. METHODS: Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and the U.K. and Republic of Ireland) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60 000 person-years of observation. 'Cases' were patients who developed an incident cancer. Patients with previous cancers and benign or in situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, sex, geographic area and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random-effects meta-analysis. RESULTS: A total of 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson Comorbidity Index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet A and smoking (the British Association of Dermatologists Biologic Interventions Register only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1·02, 95% confidence interval 0·92-1·13). Results were similar if squamous and basal cell carcinomas were included in the outcome. CONCLUSIONS: Cumulative length of exposure to biological therapies in patients with psoriasis in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use.

Biologics combined with conventional systemic agents or phototherapy for the treatment of psoriasis: real-life data from PSONET registries.

BACKGROUND: Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. OBJECTIVE: To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. METHODS: We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. RESULTS: Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43 and 92%, 28 and 83%, 65 and 87% and 53 and 77%, respectively, across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months, respectively. CONCLUSION: Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy.

Psoriatic arthritis treatment and the risk of herpes zoster.

OBJECTIVES: To study the association between traditional disease-modifying antirheumatic drugs (c-DMARD) or anti-TNF-α agents and herpes zoster (HZ) in patients with psoriatic arthritis (PsA). METHODS: A retrospective cohort study was conducted in patients with PsA between 2002 and 2013. Patients were grouped as follows: no DMARDs (Group A); c-DMARDs (Group B); anti-TNF-α agents (Group C); anti-TNF-α agents in combination with c-DMARDs (Group D). Crude incidence rates (IR) were calculated as number of HZ episodes per 1000 patient-years. A Cox regression model was used to adjust for HZ risk factors (age, gender, steroid use, Charlson Comorbidity Index score, and previous treatment) in order to estimate their contribution to the risk of the first HZ event. RESULTS: The study included 3128 patients, mean age 50.26±14.54 years; 46.2% male. During a period of 20 096 person-years 182 HZ events were observed. The crude IR (95% CI) of HZ in the study population was 9.06 per 1000 patient-years, and in Groups A-D 7.36 (5.41 to 9.79), 9.21 (7.5 to 11.21), 8.64 (4.84 to 14.26), 17.86 (10.91 to 27.58), respectively. In a multivariate analysis, age (HR 1.01, 95% CI 1.00 to 1.02), treatment with steroids (HR 1.08, 95% CI 1.04 to 1.13), and a combination of anti-TNF-α agents and c-DMARDs (HR 2.37, 95% CI 1.32 to 4.22) were significantly associated with HZ events. CONCLUSIONS: In our database, the risk of HZ was significantly increased with age, treatment with steroids, and combination of anti-TNF-α agents and c-DMARDs, but not with c-DMARDs or anti-TNF-α therapy alone. Time to HZ event was shorter in patients treated with anti -TNF-α agents.