ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 273

Long-Term Safety and Effectiveness of Adalimumab in Children with Moderately to Severely Active Polyarticular or Polyarticular-Course Juvenile Idiopathic Arthritis

Hermine Brunner1, Nicola Ruperto2, Carol A. Wallace3, Mary Toth4, Ivan Foeldvari5, John Bohnsack6, Diana Milojevic7, C. Egla Rabinovich8, Pavla Vavrincova9, Daniel J. Kingsbury10, Katherine Marzan11, Pierre Quartier12, Kirsten Minden13, Elizabeth Chalom1, Gerd Horneff14, Rolf M. Kuester15, Jason Dare16, Mareike Bereswill17, Hartmut Kupper17, Jasmina Kalabic17, Daniel Lovell18 and Alberto Martini19, 1PRCSG, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2PRINTO, Genoa, Italy, 3University of Washington School of Medicine and Seattle Children's Hospital, Seattle, WA, 4Akron Children's Hospital, Akron, OH, 5Department of Pediatric Rheumatology, Hamburger Zentrum für Kinder und Jugendrheumatologie, Hamburg, Germany, 6University of Utah, Department of Pediatrics, Salt Lake City, UT, 7Pediatrics, Division of Pediatric Rheumatology, Floating Hospital for Children at Tufts Medical Center, Boston, MA, 8Duke University Medical Center, Durham, NC, 9Fakultni nemocnice v Motole, Praha, Czech Republic, 10Randall Children's Hospital at Legacy Emanuel, Portland, OR, 11Children's Hospital Los Angeles, Los Angeles, CA, 12Pediatric Rheumatology, IMAGINE Institute, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Université Paris-Descartes, Paris, France, 13Kinderklinik der Charite, Otto-Heubner Centrum, Berlin, Germany, 14Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany, 15Asklepios Rheumazentrum Hamburg, Hamburg, Germany, 16Arkansas Children’s Hospital, Little Rock, AR, 17AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, 18Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, 19PRINTO-IRCCS, Genova, Italy

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects: Juvenile Idiopathic Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases of childhood. Adalimumab (ADA) is approved for moderate to severe polyarticular JIA (pJIA) in patients (pts) ≥4 years (yrs) in the US, Australia, and Japan and in the EU for pts ≥2 yrs. The study objective was to evaluate long-term safety and effectiveness of ADA in pts with moderately to severely active pJIA who are prescribed and treated with ADA in routine clinical practice. 5 yr interim data will be presented.

Methods: This is an ongoing, multicenter, non-interventional, observational registry of pts with moderately to severely active pJIA who are treated with either ADA±methotrexate (MTX) or MTX alone as part of their routine clinical care. 800 pts (500 in ADA arm/300 in MTX arm) were to be enrolled in the US, EU, and Australia. The follow-up observational period is 10 yrs from enrollment into one of the treatment arms. Observational adverse events (AEs) were recorded from the first day in the registry through last contact, irrespective of the duration of registry treatment. Clinical outcomes were assessed by 27-joint juvenile arthritis disease activity score (JADAS27), based on C-reactive protein (CRP).

Results: As of January 2014, enrollment is complete. 842 pts (540 in ADA arm/302 in MTX arm) were treated in the registry as of the March 28, 2014 cutoff date. The mean pJIA disease duration at registry enrollment was 1.3 and 3.7 yrs and the mean duration days of study exposure was 643 and 653 for MTX and ADA arms, respectively. At baseline, mean AJC73 was 5.8 and 5.4 for MTX and ADA, respectively, and childhood health assessment questionnaire disability index (CHAQ-DI) was 0.6 for both groups. Overall, 153 pts (50.7%) in the MTX arm and 132 pts (24.4%) in the ADA arm discontinued registry drug. Of those, 22 (7.3%) and 23 (4.3%) pts in the MTX and ADA arm, respectively, discontinued due to an AE, and 39 of the 153 pts in the MTX arm discontinued as they switched to the ADA arm of the registry. The observational AEs are summarized in the Table. No deaths, malignancies, or opportunistic infections were reported. In the ADA arm, there were 13 (2.4%) pts with serious infectious AEs (including abdominal abscess, acute tonsillitis, appendicitis, cellulitis, gastroenteritis, mononucleosis, viral meningitis, pneumonia, pyelonephritis, scarlet fever, subcutaneous abscess, tonsillitis, urinary tract infection, and varicella). Frequencies and rates of treatment-emergent AEs were similar to those reported for observational AEs. Mean JADAS27 improved from 12.1 at baseline to 9.4, 6.1, 5.1, 4.4 at  months 1, 3, 6, and 12 for pts in the MTX arm and from 12.1 at baseline to 7.4, 5.5, 4.4, 4.5 in the ADA arm, respectively (observed data).

Table. Overview of Observational Adverse Events (AEs)

 

MTX

ADA ± MTX

N=302

n (%)

PYs=863.9

E (E/100 PYs)

N=540

n (%)

PYs=1226.8

E (E/100 PYs)

Any AE

135 (44.7)

351 (40.6)

169 (31.3)

447 (36.4)

At least “possibly drug related” per the investigator

68 (22.5)

121 (14.0)

80 (14.8)

147 (12.0)

Severe AE

11 (3.6)

15 (1.7)

19 (3.5)

31 (2.5)

Serious AE

17 (5.6)

26 (3.0)

35 (6.5)

56 (4.6)

AE leading to discontinuation of study drug

20 (6.6)

26 (3.0)

27 (5.0)

39 (3.2)

Infectious AE

75 (24.8)

133 (15.4)

93 (17.2)

149 (12.1)

Serious infectious AE

8 (2.6)

11 (1.3)

13 (2.4)

15 (1.2)

Injection site-related AE

6 (2.0)*

8 (0.9)

24 (4.4)

29 (2.4)

 E, events; PYs, patient years.

*3 patients experienced injection site-related AEs with etanercept injections.

 

Conclusion: Overall, ADA is well-tolerated in these pts with active pJIA.  No new safety signals were observed, and based on this interim analysis, the known safety profile of ADA remains unchanged.

Disclosure:

H. Brunner,

AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Boehringer-Ingelheim, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UCB, and Genentech,

5,

Genentech Pharmaceuticals,

8;

N. Ruperto,

full-time employee of the GASLINI Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, ,

3,

Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, Janssen Biologics B.V., MedImmune, Roche, and Wyeth/Pfizer,

8;

C. A. Wallace,

Pfizer and Amgen ,

2,

Amgen and Novartis,

5;

M. Toth,
None;

I. Foeldvari,

AbbVie and Novartis,

9;

J. Bohnsack,

Novartis Pharmaceutical Corporation,

5;

D. Milojevic,

Genentech and Novartis,

5;

C. E. Rabinovich,

UCB Pharma, Janssen Research & Development, LLC, Hoffmann-La Roche Inc., and AbbVie,

9;

P. Vavrincova,
None;

D. J. Kingsbury,

AbbVie,

9;

K. Marzan,

AbbVie,

2;

P. Quartier,

AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum,

2,

AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum,

5;

K. Minden,

Pfizer and Abbvie,

2,

Pfizer, Abbvie, Roche/Chugai, Novartis, Medac and Pharm-Allergan,

5;

E. Chalom,

AbbVie,

8;

G. Horneff,

AbbVie, Pfizer, and Roche,

2,

AbbVie, Novartis, Pfizer, and Roche,

8;

R. M. Kuester,

AbbVie Inc. and Wyeth/Pfizer,

9;

J. Dare,

AbbVie, AstraZeneca, Horizon Pharma, and Medac GmbH,

9;

M. Bereswill,

AbbVie,

1,

AbbVie,

3;

H. Kupper,

AbbVie,

1,

AbbVie,

3;

J. Kalabic,

AbbVie,

1,

AbbVie,

3;

D. Lovell,

AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma, and Genentech,

5,

Wyeth Pharmaceuticals,

8,

Amgen and Forest Research,

9;

A. Martini,

full-time employee of the GASLINI Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, ,

3,

Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, and MedImmune,

8.

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-safety-and-effectiveness-of-adalimumab-in-children-with-moderately-to-severely-active-polyarticular-or-polyarticular-course-juvenile-idiopathic-arthritis/