PSOLAR, the Psoriasis Longitudinal Assessment and Registry, is a multicenter, longitudinal, intercontinental, disease-based registry used to identify adverse events from commonly used psoriasis drugs.1 An evaluation of the risk of serious infection from systemic psoriasis treatments was recently published using data from PSOLAR. Ninety-three institutional review boards or ethics committees reported into the registry from regions that included North America, Europe, the Middle East and Latin America. Data were collected from June 20, 2007, through Aug. 23, 2013.
Serious adverse events were submitted and evaluated in real time. Collection of data occurred at entry into the registry and for approximately six months. Results from PSOLAR suggest a higher risk of serious adverse events. Patients receiving the biologics adalimumab, etanercept, infliximab and ustekinumab were evaluated in separate cohorts and statistically analyzed. Other agents that were either investigational, no longer available, not currently indicated for psoriasis or not used enough to perform statistical analysis were not evaluated. These agents included abatacept, alefacept, briakinumab, brodalumab, certolizumab pegol, efalizumab, golimumab and secukinumab. Some of the nonbiologic therapies included methotrexate (MTX), systemic retinoids, and psoralen plus UVA and UVB. Serious infections were defined as having at least one of the following criteria: death, a life-threatening condition, persistent or significant disability or incapacitation, causing or prolonging hospitalization, or causing or prolonging another medically important condition.
Overall, 11,466 psoriatic patients were analyzed. 9,145 patients received a biologic agent, 490 received MTX and possibly other non-biologics, and 1,610 patients did not receive MTX or biologics. Cumulative incidence rates of serious infections were 1.45 per 100 patient-years (n = 323) across treatment cohorts. Individual drug/class rates were 0.83 per 100 patient-years for ustekinumab, 1.47 per 100 patient-years for etanercept, 1.97 per 100 patient-years for adalimumab and 2.49 per 100 patient-years for infliximab. Rates of serious infections in the non-biologics cohorts were 1.05 per 100 patient-years for non-MTX/non-biologics and 1.28 per 100 patient-years for the MTX/non-biologics cohorts. Infections with adalimumab and infliximab were comparable to infections with non-MTX/non-biologic therapies. No increased risk was observed with etanercept or ustekinumab treatment.
Pneumonia and cellulitis were the most common types of serious infections. Isolated incidents of necrotizing fasciitis (n = 4), tuberculosis (n = 2), histoplasmosis (n = 2), hepatitis C (n = 1) and salmonella bacteremia (n = 1) were reported. Overall, six patients developed serious infections that resulted in death. Increased risk of serious infection was associated with the following demographics: increased age, diabetes mellitus, smoking, a significant history of infection, infliximab exposure and adalimumab exposure.
Despite Setbacks, Brodalumab Trials Continue
Brodalumab, an interleukin (IL) 17 inhibitor, is currently in early clinical trials (Phase 1b and Phase 2) for a number of different autoimmune diseases.2 Amgen recently terminated its co-development and commercialization agreement with AstraZeneca for the brodalumab investigational program in trials for moderate to severe plaque psoriasis, psoriatic arthritis and axial spondyloarthritis. Amgen’s decision to sever ties with AstraZeneca for this compound was due to the potential for restrictive labeling (if approved) because of suicidal ideation and suicidal behavior already identified in brodalumab trials. AstraZeneca continues to investigate this agent.3
As of April 24, 2015, AstraZeneca’s plan was to have Amgen submit the New Drug Application in 2015 or 2016. There is a good chance this application will be delayed.
Three clinical trials have been completed investigating brodalumab for managing moderate to severe plaque psoriasis (n=4,342). The moderate to severe plaque psoriasis trials were either placebo controlled or used an active treatment arm (ustekinumab 45 mg or 90 mg). Endpoints at Week 12 included PASI and static physician’s global assessment (sPGA). In the placebo-controlled trial, brodalumab treatment led to significant improvements in clinical and patient reported outcomes.4 Open-label extensions for these studies are ongoing.
Three clinical trials for psoriatic arthritis (n=1,281) are ongoing. These trials compare two strengths of subcutaneous brodalumab (140 mg or 210 mg) to placebo. The primary endpoint of these trials is the ACR20 response at Week 16. A secondary endpoint in one of the three studies is a radiographic joint assessment and PASI 75, HAQ-PI and PSI. Estimated completion of all three of the psoriatic arthritis trials is expected in the first quarter of 2016.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
References
- Kalb RE, Florentino DF, Lebwohl MG, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: Results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 13 May 2015. doi: 10.1001/jamadermatol.2015.0718. [Epub ahead of print]
- Amgen. News Release: Amgen to terminate participation in co-development and commercialization of brodalumab. 2015 May 22.
- AstraZeneca. AstraZeneca Clinical Trials Appendix Anti-IL-17RA (brodalumab) Psoriasis & psoriatic arthritis development programmes. 2015 April 24.
- Papp K, Reich K, Leonardi C, et al. Efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis: Results of AMAGINE-1, a Phase 3, randomized, double-blind, placebo-controlled study through week 12. 2015. J Amer Acad Dermatol. May;72(5):AB233–275.
