In the Journals

IL-12/23 inhibitors linked to lower infection risk than TNF, IL-17 inhibitors in PsA, psoriasis

G. Caleb Alexander

Patients with psoriasis or psoriatic arthritis who are newly treated with IL-12/23 blockers demonstrated a reduced risk for serious infection compared with those who received TNF or IL-17 inhibitors, according to data published in Annals of the Rheumatic Diseases.

“Biologics are increasingly used for psoriasis, psoriatic arthritis and a host of other autoimmune diseases,” G. Caleb Alexander, MD, MS, of the Johns Hopkins University Bloomberg School of Public Health, told Healio Rheumatology. “These products offer great promise for many individuals with moderate or severe disease who have failed first-line treatments. However, relatively little is known about their real-world safety. In addition, all too often, studies that are performed examine the safety of individual products rather than comparing the safety of products against one another.”

To evaluate whether IL-17, IL-12/23 or TNF inhibitors are associated with an increased risk for serious infection in real-world patients with psoriasis or PsA, Li and colleagues conducted a retrospective study of commercial insurance information from Optum Labs Data Warehouse. According to the researchers, the database includes admissions claims for more than 100 million patients of all ages, races and ethnic groups, in all 50 states. For their study, the researchers focused on prescription dispensations or infusion claims for any biologics of interest between Jan. 1, 2015, and May 1, 2018. A total of 11,560 treatment initiations were included.

Treatments included in the study were the IL-17 blockers ixekizumab (Taltz, Eli Lilly) and secukinumab (Cosentyx, Novartis); the IL-12/23 inhibitor ustekinumab (Stelara, Janssen); and the TNF inhibitors adalimumab (Humira, AbbVie), certolizumab pegol (Cimzia, UCB), etanercept (Enbrel, Amgen), golimumab (Simponi, Janssen) and infliximab (Remicade, Janssen).

Hospital beds 
Patients with psoriasis or PsA who are newly treated with IL-12/23 blockers demonstrated a reduced risk for serious infection compared with those who received TNF or IL-17 inhibitors, according to data.
Source: Adobe

However, the IL-17 blocker brodalumab (Kyntheum, LEO Pharma) and the IL-12/23 inhibitor guselkumab (Tremfya, Janssen) were not included, as they were approved by the FDA only toward the end of the study period. The primary outcome was infection leading to hospitalization following treatment initiation.

According to the researchers, 190 serious infections, representing 2% of all treatment episodes, were identified among 9,264 person-years of follow-up. Although class-specific incidence rates for serious infection were similar among IL-17 and TNF inhibitors, they were significantly lower for IL-12/23 blockers. After adjustment for propensity scores, there was no increased risk associated with IL-17 inhibitors compared with either TNF (HR = 0.89; 95% CI, 0.48-1.66) or IL-12/23 (HR = 1.12; 95% CI, 0.62-2.03) inhibitors. Still, IL-23/23 inhibitors were associated with a lower risk of serious infections compared with TNF inhibitors (HR = 0.59; 95% CI, 0.39-0.9).

“Interestingly, in biologic-experienced individuals there was no difference in infection risk across TNF, IL-17 or IL-12/23 inhibitors,” Alexander said. “Furthermore, relative to TNF and IL-17 inhibitors, IL-12/23 inhibitors were associated with a reduced risk of serious infection in biologic-naïve patients.”

“These results are important because biologics play a growing role in the treatment of these and other chronic conditions, and relatively little is known about their comparative safety,” he added. “It’s important to keep in mind that we examined just one of many potential adverse events, and clinicians and patients must balance the potential risks of these products with their costs, effectiveness and other product characteristics.” – by Jason Laday

Disclosure: Alexander reports being a past chair of FDA’s Peripheral and Central Nervous System Advisory Committee, that he has served as a paid advisor to IQVIA, and that he is a consultant and holds equity in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation. He is also a member of OptumRx’s National P&T Committee.

G. Caleb Alexander

Patients with psoriasis or psoriatic arthritis who are newly treated with IL-12/23 blockers demonstrated a reduced risk for serious infection compared with those who received TNF or IL-17 inhibitors, according to data published in Annals of the Rheumatic Diseases.

“Biologics are increasingly used for psoriasis, psoriatic arthritis and a host of other autoimmune diseases,” G. Caleb Alexander, MD, MS, of the Johns Hopkins University Bloomberg School of Public Health, told Healio Rheumatology. “These products offer great promise for many individuals with moderate or severe disease who have failed first-line treatments. However, relatively little is known about their real-world safety. In addition, all too often, studies that are performed examine the safety of individual products rather than comparing the safety of products against one another.”

To evaluate whether IL-17, IL-12/23 or TNF inhibitors are associated with an increased risk for serious infection in real-world patients with psoriasis or PsA, Li and colleagues conducted a retrospective study of commercial insurance information from Optum Labs Data Warehouse. According to the researchers, the database includes admissions claims for more than 100 million patients of all ages, races and ethnic groups, in all 50 states. For their study, the researchers focused on prescription dispensations or infusion claims for any biologics of interest between Jan. 1, 2015, and May 1, 2018. A total of 11,560 treatment initiations were included.

Treatments included in the study were the IL-17 blockers ixekizumab (Taltz, Eli Lilly) and secukinumab (Cosentyx, Novartis); the IL-12/23 inhibitor ustekinumab (Stelara, Janssen); and the TNF inhibitors adalimumab (Humira, AbbVie), certolizumab pegol (Cimzia, UCB), etanercept (Enbrel, Amgen), golimumab (Simponi, Janssen) and infliximab (Remicade, Janssen).

Hospital beds 
Patients with psoriasis or PsA who are newly treated with IL-12/23 blockers demonstrated a reduced risk for serious infection compared with those who received TNF or IL-17 inhibitors, according to data.
Source: Adobe

However, the IL-17 blocker brodalumab (Kyntheum, LEO Pharma) and the IL-12/23 inhibitor guselkumab (Tremfya, Janssen) were not included, as they were approved by the FDA only toward the end of the study period. The primary outcome was infection leading to hospitalization following treatment initiation.

According to the researchers, 190 serious infections, representing 2% of all treatment episodes, were identified among 9,264 person-years of follow-up. Although class-specific incidence rates for serious infection were similar among IL-17 and TNF inhibitors, they were significantly lower for IL-12/23 blockers. After adjustment for propensity scores, there was no increased risk associated with IL-17 inhibitors compared with either TNF (HR = 0.89; 95% CI, 0.48-1.66) or IL-12/23 (HR = 1.12; 95% CI, 0.62-2.03) inhibitors. Still, IL-23/23 inhibitors were associated with a lower risk of serious infections compared with TNF inhibitors (HR = 0.59; 95% CI, 0.39-0.9).

“Interestingly, in biologic-experienced individuals there was no difference in infection risk across TNF, IL-17 or IL-12/23 inhibitors,” Alexander said. “Furthermore, relative to TNF and IL-17 inhibitors, IL-12/23 inhibitors were associated with a reduced risk of serious infection in biologic-naïve patients.”

“These results are important because biologics play a growing role in the treatment of these and other chronic conditions, and relatively little is known about their comparative safety,” he added. “It’s important to keep in mind that we examined just one of many potential adverse events, and clinicians and patients must balance the potential risks of these products with their costs, effectiveness and other product characteristics.” – by Jason Laday

Disclosure: Alexander reports being a past chair of FDA’s Peripheral and Central Nervous System Advisory Committee, that he has served as a paid advisor to IQVIA, and that he is a consultant and holds equity in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation. He is also a member of OptumRx’s National P&T Committee.