New psoriatic patients may have lower serious infection risk with IL-12/23 inhibition

Biologic-naive patients with psoriasis or psoriatic arthritis had a lower risk of serious infection with interleukin-12/23 (IL-12/23) inhibitors than they did with tumor necrosis factor (TNF) inhibitors, but this difference disappeared in patients with previous exposure to biologics, according to data from a retrospective study of nearly 10,000 adults.

Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.

The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.

Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.

The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.

After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).

The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.

However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.

The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
 

SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.

Biologic-naive patients with psoriasis or psoriatic arthritis had a lower risk of serious infection with interleukin-12/23 (IL-12/23) inhibitors than they did with tumor necrosis factor (TNF) inhibitors, but this difference disappeared in patients with previous exposure to biologics, according to data from a retrospective study of nearly 10,000 adults.

Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.

The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.

Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.

The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.

After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).

The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.

However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.

The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
 

SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.

Biologic-naive patients with psoriasis or psoriatic arthritis had a lower risk of serious infection with interleukin-12/23 (IL-12/23) inhibitors than they did with tumor necrosis factor (TNF) inhibitors, but this difference disappeared in patients with previous exposure to biologics, according to data from a retrospective study of nearly 10,000 adults.

Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.

The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.

Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.

The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.

After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).

The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.

However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.

The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
 

SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.