Table 4. Studies assessing safety of bDMARDs in patients with JIA.
| Author | Year Published | Data Source | Patient Population | Sample Size | Serious Infections | Malignancies | Other Adverse Events |
|---|---|---|---|---|---|---|---|
| Horneff et al. (48) | 2016 | German BIKER Registry | JIA | 3,695 JIA patients, totaling 13,198 observation years, the analysis spanning until December 31, 2015 | NA | 1 patients had received MTX, while 9 patients were exposed to bDMARDs: 1 received ETA, 6 received ETA+MTX, 1 received ETA+ADA+MTX, and one patient underwent a sequence of treatments with MTX, ADA, ETA, INF and ABA. A total of 12 suspected cases of malignancies were identified, with 7 being lymphomas. Use of etanercept did not appear to further elevate the risk. | NA |
| Beukelman et al. (46) | 2016 | Medicaid claim database | JIA | 3,075 new MTX users, 2,713 new TNFi users and 247 new ANA users | No increased risk of hospitalized infection by all organisms associated with TNFi monotherapy or with TNFi+MTX combination therapy vs. MTX (adjusted hazard ratio (aHR) 1.19, 95% CI: 0.72, 1.94; 1.23, 95% CI: 0.69, 2.17, respectively). Baseline high-dose oral glucocorticoid was associated with infection (aHR 2.03, 95% CI: 1.21, 3.39). | NA | NA |
| Becker et al. (42) | 2017 | German BIKER Registry | JIA | 3,350 patients for 5,919 observation-years | Treatment with ETA or ADA slightly increased the risk of serious infections compared to MTX among these patients (MTX vs. ETA vs. ADA = 1.6 vs. 8.1 vs. 9.7/1,000 person-years). | NA | NA |
| Beukelman et al. (49) | 2018 | Medicaid and MarketScan claims database | JIA, pediatric inflammatory bowel disease (pIBD) and pediatric plaque psoriasis (pPsO) | 15,598 children with TNFi use and 73,839 with no TNFi use | NA | There was no significantly increased risk of malignancy among children undergoing treatment with TNFi compared to those receiving other treatments. However, it did show a doubled risk of malignancy in children with JIA overall when compared to an age-matched control of patients with an unrelated condition (standardized incidence risk (SIR): JIA + TNFi: 3.1 (95% CI: 1.3-6.1), JIA without TNFi: 2.1 (95% CI: 1.1-3.5), Control: 0.97 (95% CI: 0.91-1.05). | NA |
| Lee et al. (47) | 2018 | MarketScan claims database | JIA | 482 TNFi initiators and 2013 csDMARD initiators; TNFis included ETA, ADA, INF, CER, GOL, csDMARDs included MTX, hydroxychloroquine (HCQ), sulfasalazine (SSZ) and leflunomide (LEF)) | TNFi initiators were associated with an increased risk of serious bacterial infection compared with csDMARDs initiators (aHR 2.72, 95% CI: 1.08-6.86), adjusting for potential confounders obtained through high-dimensional propensity scores (HDPS) method and time-varying corticosteroid use. | NA | NA |
| Brunner et al. (45) | 2020 | STRIVE Registry | Polyarticular JIA | 838 patients (MTX 301; ADA ± MTX 537)* | Serious infection rates were slightly higher in the ADA ± MTX arm (MTX: 1.5 events/100 patient-years; ADA ± MTX: 2.0 evens/100 patient-years). ADA ± MTX is well tolerated. | NA | Common AEs included nausea, sinusitis, and vomiting for MTX monotherapy while arthritis, upper respiratory tract infection, sinusitis, tonsillitis, and injection site pain reported in the ADA ± MTX patients. |
| Klein et al. (43) | 2020 | German BIKER Registry | Polyarticular JIA | 3,873 patients with a cumulative exposure to bDMARDs of 7467 years | No significant differences in occurrence of medically important infections were found between patients receiving any TNFi and patients receiving TOC (RR = 0.85, 95% CI: 0.27-2.70). | Eight cases of malignancy were reported but the significance remains unclear. | The most common AEs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequently reported for patients on TOC. |
| Thiele et al. (44) | 2021 | German BIKER Registry | JIA | 3,258 patients - TNFi 3044, IL-1i 105, IL- 6i 400 and T-cell activation inhibitors 105 | Patients treated with IL-1i or IL-6i reported significantly more infections (IR = 17.3, 95% CI: 12.5-24; IR = 16.7, 95% CI: 13.9-20), compared with patients treated with TNFi (IR = 8.7, 95% CI: 8.1-9.4). Infections classified as SAEs also occurred more frequently in the IL-1i or IL-6i cohorts. | NA | Incidence of herpes zoster and varicella was higher in patients on TNFi. Other opportunistic infections were rare. |
| Thiele et al. (32) | 2023 | German BIKER Registry | Polyarticular JIA | 2,148 Patients (684 bDMARDs monotherapy, 1,464 combination with MTX); bDMARDs included ADA, ETA, GOL, and TOC | NA | NA | 1,757 AEs reported, most commonly viral upper respiratory infections, GI disorders (e.g. nausea), and transaminase elevation, with 116 classified as SAEs. A higher incidence of AEs in patients on combination therapy was observed. No significant differences in the rate of SAEs between the two groups. |
*Outcomes were not statistically powered.