170 Safety and efficacy of subcutaneous tocilizumab in patients with systemic and polyarticular juvenile idiopathic arthritis
Bibliographic record
Abstract
Background: As intravenous (IV) tocilizumab (TCZ) has been shown to improve disease symptoms in patients with polyarticular (p)JIA/systemic (s)JIA, an ongoing 5-year, long-term extension (LTE) (NCT02165345) of two 52-week, open-label studies (NCT01904279/NCT01904292) will evaluate long-term safety and efficacy of subcutaneous (SC) TCZ. Methods: PJIA patients aged 1-17 years received TCZ 162 mg every 3 weeks (Q3W) for body weight (BW) <30 kg or every 2 weeks (Q2W) for BW ⩾ 30 kg; sJIA patients received TCZ 162 mg Q2W for BW < 30 kg (or every 10 days (Q10D)) or weekly (QW) for BW ⩾ 30 kg. pJIA patients had failed or could not tolerate MTX treatment and sJIA patients had inadequate response to NSAIDs and glucocorticoids. All patients had to discontinue biologic DMARDs (except TCZ IV, which was switched to SC). After 52 weeks, eligible patients continued TCZ treatment according to BW in the LTE; we report LTE safety data for pJIA/sJIA. Results: Adverse event (AE) rates (Table 1) were similar regardless of BW. Most AEs were grade 1/2; grade ⩾3 AEs were reported by 10/44 (20.8%) pJIA patients and 4/38 (10.5%) sJIA patients. The most common AE was nasopharyngitis in both pJIA (17/44 [38.6%]) and sJIA (11/38 [28.9%]). Other AEs reported in ⩾ 15% of patients were arthralgia, gastroenteritis, cough, vomiting, diarrhoea, pyrexia, headache, and oropharyngeal pain in pJIA, and upper respiratory tract infection, cough, pyrexia, arthralgia, and rash in sJIA. AEs of special interest (AESIs) were consistent with the 52-week data, and no opportunistic infections developed. Neutropaenia AEs were reported by 6 pJIA patients (13.6%) and 7 sJIA patients (18.4%). Of pJIA patents, 5/44 (11.4%) experienced SAEs (furuncle, appendicitis, pneumonia, eye pain/headache, infectious mononucleosis); only pneumonia was considered treatment related. Of sJIA patients, 2/38 (5.3%) experienced SAEs (pneumonia, craniocerebral injury from a fall); neither was considered treatment related. Neutralising anti-TCZ antibodies developed in 2 pJIA patients (4.7%) and 0 sJIA patients. No deaths were reported in the LTE to the data cutoff. Conclusion: In this long-term extension study of SC TCZ in children with pJIA or sJIA, TCZ continues to have an acceptable tolerability profile with no new safety concerns. Safety summary AEs, adverse events; CI, confidence interval; pJIA, polyarticular juvenile idiopathic arthritis; PY, patient-years; Q2W, every 2 weeks; Q3W, every 3 weeks; Q10D, every 10 days; SAEs, serious adverse events; SC, subcutaneous; sJIA, systemic juvenile idiopathic arthritis; TCZ, tocilizumab. Disclosures: A.V. Ramanan: Member of speakers’ bureau; AbbVie, UCB, SOBI, Lily. H.I. Brunner: Consultancies; Roche, BMS, Novartis, Pfizer, R-Pharm, Celgene, AstraZeneca, Jannsen, Ablynx, GSK, Takeda, Sanofi. Member of speakers’ bureau; Roche, Novartis, Pfizer. Other; Roche, Novartis, Pfizer, BMS. N. Ruperto: Consultancies; Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, CD-Pharma, Celgene, CrescendoBio, EMD Serono, Hoffmann-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, NovoNordisk, Pfizer, Rewind Arms, R-Ph. Grants/research support; Abbott, BMS. A. Martini: None. R.J. Cuttica: None. J.E. Weiss: None. M. Henrickson: None. H. Schmeling: Grants/research support; Roche. J. Antón: Consultancies; AbbVie, Alexion, BMS, Gebro, Novartis, Pfizer, Roche, Sobi. Honoraria; AbbVie, Alexion, BMS, Gebro, Novartis, Pfizer, Roche, Sobi. Member of speakers’ bureau; AbbVie, Alexion, BMS, Gebro, Novartis, Pfizer, Roche, Sobi. Grants/research support; AbbVie, Alexion, Amgen, BMS, ChemoCentryx, Novartis, Novimmune, Roche, Sanofi, Pfizer. K. Minden: Consultancies; AbbVie, Sanofi, Medac, MedCon. Grants/research support; Pfizer, AbbVie, Roche. G. Horneff: Consultancies; Abbvie, Chugai, Roche, BMS, Novartis, Pfizer, Celgene, MSD, Ablynx. M. Gámir-Gámir: None. M. Hufnagel: None. W. Douglass: Corporate appointments; Roche. Shareholder/stock ownership; Roche. C. Wells: Corporate appointments; Roche. S. Wimalasundera: Corporate appointments; Roche. Shareholder/stock ownership; Roche. N.L. Mallalieu: Corporate appointments; Roche. Shareholder/stock ownership; Roche. D.J. Lovell: Consultancies; AstraZeneca, Amgen, Abbott, Pfizer. Member of speakers’ bureau; Wyeth. F. De Benedetti: Grants/research support; Abbvie, Sobi, Novimmune, Roche, Novartis, Sanofi, UCB, Pzifer.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".