Open-label, Long-term (10-year) Study of the Safety of Etanercept in Children with Extended Oligoarticular Arthritis, Enthesitis-related Arthritis, or Psoriatic Arthritis

Jelena Vojinović¹, Joke Dehoorne², Violeta Panaviene³, Gordana Susic⁴, Gerd Horneff⁵, Valda Stanevicha⁶, Katarzyna Kobusinska⁷, Zbigniew Zuber⁸, Bogna Dobrzyniecka⁹, Jonathan Akikusa¹⁰, Tadej Avcin¹¹, Alberto Martini¹², Cecilia Borlenghi¹³, Edmund Arthur¹⁴, Svitlana Tatulych¹⁵, Chuanbo Zang¹⁶, Bonnie Vlahos¹⁶ and Nicolino Ruperto¹⁷, ¹Paediatric Rheumatology International Trials Organisation (PRINTO), Nis, Serbia, ²Paediatric Rheumatology International Trials Organisation (PRINTO), Gent, Belgium, ³Paediatric Rheumatology International Trials Organisation (PRINTO), Vilnius, Lithuania, ⁴Paediatric Rheumatology International Trials Organisation (PRINTO), Belgrade, Serbia, ⁵Paediatric Rheumatology International Trials Organisation (PRINTO), Sankt Augustin, Germany, ⁶Paediatric Rheumatology International Trials Organisation (PRINTO), Riga, Latvia, ⁷Paediatric Rheumatology International Trials Organisation (PRINTO), Bydgoszcz, Poland, ⁸Paediatric Rheumatology International Trials Organisation (PRINTO), Lodz, Poland, ⁹Paediatric Rheumatology International Trials Organisation (PRINTO), Warsaw, Poland, ¹⁰Paediatric Rheumatology International Trials Organisation (PRINTO), Melbourne, Australia, ¹¹Paediatric Rheumatology International Trials Organisation (PRINTO), Ljubljana, Slovenia, ¹²Paediatric Rheumatology International Trials Organisation (PRINTO), Genoa, Italy, ¹³Pfizer, Buenos Aires, Argentina, Buenos Aires, Argentina, ¹⁴Pfizer, Peapack, NJ, ¹⁵Pfizer, Groton, CT, ¹⁶Pfizer, Collegeville, PA, ¹⁷IRCCS Istituto Giannina Gaslini; PRINTO, Clinica Pediatrica e Reumatologia, Genova, Italy

Meeting: ACR Convergence 2021

Keywords: clinical trial, etanercept, Juvenile idiopathic arthritis, Long-term, Safety

Session Information

Date: Saturday, November 6, 2021

Title: Pediatric Rheumatology – Clinical Poster I: JIA (0241–0265)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: CLIPPER2 was an 8-year, open-label extension of the phase 3b, multicenter, 2-year CLIPPER study of the safety and efficacy of etanercept (ETN) in the treatment of patients (pts) with juvenile idiopathic arthritis (JIA) categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). The objective of this analysis was to describe the safety of ETN in this population after 10-years of follow up.

Methods: Pts (n=127) with eoJIA (2-17 years), ERA, or PsA (each 12-17 years) who received ≥1 ETN dose (0.8 mg/kg once weekly [max, 50 mg]) in CLIPPER were eligible to enter CLIPPER2. The primary outcome measure was the occurrence of malignancy. Long-term safety was assessed as the total incidence of events from CLIPPER baseline (BL) to month (m) 120, frequency of events per 100 patient-years (EP100PY), and frequency of events in each study year.

Results: A total of 109/127 (86%) pts entered CLIPPER2; 99 (91%) continued in the active treatment period. At m120, 84/109 (77%) pts had completed the study; 27 (25%) while actively taking ETN, 7 (6%) had withdrawn from treatment due to low/inactive disease; 5 (5%) had re-started ETN following an earlier withdrawal from treatment; and 45 (41%) had stopped ETN (but remained under observation) (Figure 1); 25/109 (23%) pts permanently discontinued from the CLIPPER2 study.

In CLIPPER/CLIPPER2, 1 case of malignancy (Hodgkin’s disease) was reported (1 pt with eoJIA in year 3). There was 1 case of uveitis (1 pt with eoJIA in year 8) and 3 of Crohn’s disease (2 pts with ERA, year 1/year 6; 1 pt with eoJIA, year 5). There were 2 cases of opportunistic infections (both herpes zoster), and no deaths. Overall, there were 559 (81.82 EP100PY) treatment-emergent adverse events (TEAEs) excluding infections and injection-site reactions (ISRs). The overall rate of TE serious infections was low (N=14; 2.05 EP100PY) (Table), with the most common TE serious infection being gastroenteritis (N=2; 0.29 EP100PY). The most frequently reported TEAEs (N [EP100PY]) were headache (28 [4.10]), arthralgia (24 [3.51]), pyrexia (21 [3.07]), diarrhea (14 [2.05]), and leukopenia (12 [1.76]). Overall, 39 patients reported serious TEAEs (excluding infections/ISRs).

The number and frequency (N [EP100PY]) of TEAEs (excluding infections/ISRs) decreased over the 10-year study period from 193 [173.81] in year 1 to 9 [27.15] in year 10. The number and frequency of TE infections and serious TE infections also decreased over the 10-year study period. There was no clear trend of a decrease over time for the incidence of serious TEAEs (Figure 2).

Conclusion: ETN treatment to m120 was well tolerated in this patient population and consistent with the known safety profile. Frequency of TEAEs and TE infections decreased over time. Over 10 years there was I reported event of malignancy and the overall rate of TE serious infections was low.

Trial Registration: NCT00962741/NCT01421069

Figure 1. Study Design and Subject Disposition

Table. ETN Safety Summary (from CLIPPER BL to m120), N (EP100PY) (FAS)*

Figure 2. Incidence of TEAEs (A) and TE Infections (B) in CLIPPER/CLIPPER2 by Study Year, N (EP100PY)

Disclosures: J. Vojinović, Abbvie, 6, Roche, 6, Sandoz, 6; J. Dehoorne, Abbvie, 2, 6, Roche, 2, 6; V. Panaviene, None; G. Susic, None; G. Horneff, Novartis, 5, 6, Janssen, 5, 6, Roche, 5, Eli-Lilly, 6, Glaxo Smith and Kline, 6, Pfizer, 6, Sobi, 6; V. Stanevicha, Sandoz, 6, Abbvie, 6, Roche, 6, Pfizer, 2, 12, Clinical studies, BMS, 12, Clinical studies, Sanofi, 6; K. Kobusinska, None; Z. Zuber, None; B. Dobrzyniecka, None; J. Akikusa, None; T. Avcin, Abbvie, 2, 6, Alexion, 2, Octapharma, 2, 6, Takeda, 2, 6; A. Martini, Aurinia, 2, 6, Bristol Myers and Squibb, 2, 6, Eli-Lilly, 2, 6, EMD Serono, 2, 6, Janssen, 2, 6, Pfizer, 2, 6, Roche, 2, 6; C. Borlenghi, Pfizer, 3, 11; E. Arthur, Pfizer, 3; S. Tatulych, Pfizer, 3, 11; C. Zang, Pfizer, 3, 11; B. Vlahos, Pfizer, 3, 11; N. Ruperto, Ablynx, 2, 6, Amgen, 2, 6, Astrazeneca-Medimmune, 2, 6, Aurinia, 2, 6, Bayer, 2, 6, Bristol Myers and Squibb, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, Cambridge Healthcare Research (CHR, 2, 6, Celgene, 2, 6, Domain therapeutic, 2, 6, Eli-Lilly, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, EMD Serono, 2, 6, Glaxo Smith and Kline, 2, 6, Idorsia, 2, 6, Janssen, 2, 6, Novartis, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, Pfizer, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, Sobi, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, UCB, 2, 6, F Hoffmann-La Roche, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties.

To cite this abstract in AMA style:

Vojinović J, Dehoorne J, Panaviene V, Susic G, Horneff G, Stanevicha V, Kobusinska K, Zuber Z, Dobrzyniecka B, Akikusa J, Avcin T, Martini A, Borlenghi C, Arthur E, Tatulych S, Zang C, Vlahos B, Ruperto N. Open-label, Long-term (10-year) Study of the Safety of Etanercept in Children with Extended Oligoarticular Arthritis, Enthesitis-related Arthritis, or Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/open-label-long-term-10-year-study-of-the-safety-of-etanercept-in-children-with-extended-oligoarticular-arthritis-enthesitis-related-arthritis-or-psoriatic-arthritis/. Accessed .

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