Which Psoriasis Biologics Have the Best Response Rates?

Biologic drugs such as adalimumab (ADA), etanercept (ETN), infliximab (IFX), and ustekinumab (UST) have revolutionized the way we manage moderate to severe psoriasis vulgaris and psoriatic arthritis. Patients who once had debilitating disease can now enjoy clear or almost-clear skin in most cases, with many seeing dramatic improvement within 1 month of therapy. Biologics are so effective because they target specific proinflammatory pathways that are critical to the pathogenesis of psoriasis.

 

First-generation biologics (ETN, IFX, ADA) work by blocking tumor necrosis factor-alpha signaling, while second-generation biologics (UST) target the proinflammatory cytokines interleukin (IL)-12/23, and third-generation biologics target IL-17. All biologics yield superior efficacy rates (Psoriasis Area Severity Index [PASI] 75 responses ranging from 40% to > 90%) when compared with methotrexate, cyclosporine, and acitretin, with fewer adverse events and better overall tolerability. Treatment failures do occur, however; some patients do not achieve PASI 75 clearance, some experience diminished efficacy over time, and others discontinue the medication because of adverse events both mild (eg, injection-site reactions) and severe (eg, opportunistic infections).

 

Is there a way to predict real-life response rates to biologics? Placebo-controlled clinical trials with outcome measures such as PASI 75/90/100 response rates and Physician Global Assessment (PGA) scores are the best benchmarks of clinical efficacy, but these studies rarely evaluate long-term efficacy (> 4 years of follow-up). To address this deficiency, Vilarrasa and colleagues conducted a retrospective study to determine "drug survival" (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline PASI, 16.4). In addition to determining mean drug survival times for ETN, IFX, ADA, and UST, investigators searched for variables that positively or negatively affected drug survival times.

 

The cohort of 427 Spanish patients received 703 courses of biologic therapy during the study period (January 2007-June 2013). Roughly half of these patients entered the study period without previous exposure to biologic therapy. Roughly a third of patients received combination treatment, most commonly with methotrexate (76.1% of combination therapy cases). Drug survival was calculated from start to discontinuation of therapy due to primary lack of effectiveness (failure to reach PASI 75 response by week 16), secondary treatment failure (loss of PASI 50 response), or biologic-associated adverse events.

 

On the basis of their statistical analysis, the authors observed the following:

 

Overall mean drug survival for all biologics was 31.0 months.

 

Drug survival for all biologics was lower in obese patients (BMI > 30 kg/m2) versus nonobese patients (23.0 months versus 37.3 months).

 

Drug survival was longest for patients taking UST (> 48 months) versus all other biologics (ADA = 30.5 months; ETN = 24.8 months; IFX = 30.0 months).

 

Drug survival was shortest for patients taking ETN (24.8 months).

 

Dose augmentation (increasing the dose for suboptimal response) only increased drug survival in the IFX group; in contrast, combination therapy did not affect drug survival.

 

PASI 75 and PASI 90 responses at week 16 increased drug survival (45.0 months and 50.9 months, respectively).

 

Variables that did not affect drug survival included: gender, presence of psoriatic arthritis, biologic-naive status prior to treatment, and use of combination therapy.

 

 

When considering biologic therapies for patients with moderate to severe psoriasis vulgaris, clinicians have a growing list of options to choose from. "Real-life" drug survival isn't the only predictive measure of treatment success, but it should be considered along with adverse risk considerations, patient compliance, comorbidities, and, unfortunately, drug expense and insurance coverage.

 

Vilarrasa and colleagues acknowledge that their retrospective study was not randomized; hence, there may have been hidden factors influencing which biologic was chosen for which patient, and these in turn may have influenced the drug survival data. Nevertheless, their findings that drug survival was shortest for ETN and longest for UST (versus TNF-alfa inhibitors) is in agreement with findings of similar Dutch and Danish studies,[1-3] as is the observation that obesity predicts a higher likelihood of treatment failure for all biologics.[4]

 

These results should help to educate patients and to manage expectations. Patients who respond rapidly to biologic therapy (PASI 70 or PASI 90 clearance during the induction phase) are more likely to enjoy long-term remission. In contrast, those with a high BMI should be advised that their psoriasis may take longer to respond and may need combination therapy for optimal clearance.