adverse events resulting in withdrawal of geologic therapy in psoriasis

• tumor necrosis factor and interleukin 12/23 inhibitors

• emerged in recent years

• potent agents for management of moderate to severe psoriasis

• prescribed frequently and for long durations

BIOLOGIC THERAPIES

SAFETY CONSIDERATION

The most concerning adverse events

• Infection

• tuberculosis reactivation

•malignancy

Such AEs can significantly affect physician and patient reluctance to use these efficacious agents in the treatment of psoriasis.

ADVERSE EVENTS

limited to data from randomized controlled trials (RCTs)

• selective sampling of patients and constrained follow-up time

• difficult to generalize the results to much more diverse patient populations seen in clinical practice.

• RCTs trials are powered to detect efficacy rather than AEs

CURRENT KNOWLEDGE ABOUT SAFETY

METHODS

• multicenter retrospective cohort data collection

• 398 patients from 2 academic hospitals

Inclusion criteria :

1. patients with psoriasis treated with etanercept, infliximab, adalimumab, or ustekinumab;

2. patient age 18 years or older.

METHODS

METHODS

data collected:

• patient demographic information and comorbidities;

• duration of underlying disease at start of biologic therapy;

• concomitant systemic agent(s);

• current and previous biologic agent(s), dosage, dates of commencement, and discontinuation;

• reason for withdrawal of previous agent(s)

•multicenter data extraction and collection to minimize bias associated with differences between physicians and medical settings

• comparison of different biologic agents

• no industry involvement

ADVANTAGES

The AEs were stratified by thefollowing subtypes :

• injection-site reaction

• infusion reaction

• infection

• malignancy

• tuberculosis reactivation

• lupuslike symptoms

• iritis

• cardiac symptoms

• neurologic symptoms

STATISTICAL ANALYSIS

RESULTS

• The most commonly used biologic agent was ustekinumab

• Many patients received more than 1 biologic (n = 117)

• The longest median duration of therapy until withdrawal because of AE was observed with ustekinumab followed by infliximab

• In total AEs led to withdrawal of biologic therapy for an incidence rate of 1.97 events/ 100 patient-years

RESULTS

Biologic agent

100 patient-

years

etanercept 1.13

infliximab 4.96

adalimumab 2.38

ustekinumab 1.38

RESULTS

• significantly higher withdrawal rate among the infliximab users because of infusion reactions.(IV)(3% to 22% cited in the literature)

• AE rates leading to withdrawal in the study of Gniadecki et al was highest for infliximab (14.6%), as it was in another cohort of 650 Spanish patients (14.3%) and in our own cohort (15%).

• In a Danish study, AEs accounted for 12% of discontinued treatments, respectively, in comparison with 11.1% in the current study

DISCUSSION

• AEs resulting in withdrawal occurred at 4% with an incidence rate of 1.97/100 patient-years

• Infection and malignancy resulting in withdrawal accounted for less than 2% of all biologic treatments

• biologic therapies are associated with a low rate of withdrawal-related AEs in real-world clinical practice

CONCLUSIONS

• A few medical charts lacked sufficient details, which made the interpretation of their findings somewhat subjective

• patients might have been taking different agents within a short time span

• the small study population limits the conclusiveness of findings

LIMITS