Safety of biologic therapies for the treatment of juvenile idiopathic arthritis

Abstract

The safety profiles of approved biologics, the TNF-α inhibitors etanercept and adalimumab, and the IL-6-inhibitor tocilizumab are highly acceptable. This conclusion is not easily expandable to the IL-1 inhibitor canakinumab as well as the T-cell-activation-inhibitor abatacept due to lack of experience; however, both have showed an excellent safety profile so far. An increase in knowledge about risk profiles in national and international collaborations, with national as well as international registries, is necessary.

Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease

“…In an interim analysis of multiple therapies, 6 cases of new-onset psoriasis were observed in pediatric patients with JIA treated with adalimumab ± concomitant therapy in the BIKER registry (n = 552); this event was not observed in patients receiving other therapies (etanercept [n = 2000], tocilizumab [n = 108]), or methotrexate [n = 1517]). 11 In the present analysis, the rate of uveitis in pediatric patients treated with adalimumab was low across indications (0.6 events/100 PY) and among patients with JIA (0.7 events/100 PY). It should be noted that uveitis is comorbid of JIA.…”

“…Opportunistic infections are generally rare in pediatric patients treated with TNF inhibitors based on previous studies. 11,33,38,39 Worsening/new onset of psoriasis was observed in 4% of all pediatric patients treated with adalimumab in our study. In an interim analysis of multiple therapies, 6 cases of new-onset psoriasis were observed in pediatric patients with JIA treated with adalimumab ± concomitant therapy in the BIKER registry (n = 552); this event was not observed in patients receiving other therapies (etanercept [n = 2000], tocilizumab [n = 108]), or methotrexate [n = 1517]).…”

“…[11][12][13] The rates of AEs and SAEs were 64.5 and 4.9 events/100 PY, respectively, for patients treated with adalimumab ± concomitant therapy (eg, nonsteroidal anti-inflammatory drugs, corticosteroids, methotrexate, and other disease-modifying antirheumatic drugs) in an interim analysis (n = 552, 679 PY of exposure) of the Biologika in der Kinderrheumatologie Register (BIKER) JIA registry. 11 Similarly, in the 6-year interim analysis of the STRIVE registry, a multicenter, longitudinal postmarketing, observational study to assess long-term safety and effectiveness of HUMIRA (adalimumab; AbbVie Inc, North Chicago, Illinois) in children with moderately to severely active polyarticular or polyarticular-course juvenile idiopathic arthritis, patients with pJIA treated with adalimumab ± methotrexate (n = 543) had observed rates of AEs and SAEs of 43.7 and 7.5 events/100 PY, respectively. 13 Opportunistic infections, excluding oral candidiasis and TB, were low in our analysis, consistent with findings in adults treated with adalimumab across multiple indications, 10 and occurred only in pediatric patients with CD.…”

“…An analysis of adverse event (AE) data across multiple indications from 23 458 patients (mostly adults), some of whom had clinical trial exposure to adalimumab for almost 12 years, found that although rates of specific AEs varied by disease, the overall safety profile was consistent with that of anti-TNF agents as a class 10 ; no new safety signals were identified. Although interim data from ongoing pediatric registries for pJIA, CD, and psoriasis are emerging, [11][12][13][14][15] pediatric safety data for adalimumab remain limited relative to adult safety data. Therefore, examining safety data within and across multiple therapeutic areas specifically in pediatric populations from controlled clinical trials may provide additional, valuable safety information.…”

Unintended Immunological Consequences of Biologic Therapy

“…Mtb reactivation has also been reported although at a lower rate than with TNFis and screening for tuberculosis is recommended [1, 16]. Other adverse immune effects observed with tocilizumab include some cases of neutropenia that were not associated with serious infections [10, 17, 16] Finally, in trials for SJIA, there were reports of episodes of macrophage activation syndrome (MAS) upon withdrawal of drug, although SJIA patients have an overall increased rate of MAS [17]. There are a significant number of biologics targeting IL-6 currently in trials (Table 2) and based on the mechanism of action of this cytokine, other possible immunological derangements include a spectrum of infections similar to deficiencies that result in Th17 defects as each biologic will likely have differing off target effects.…”