Newswise — A combination of infliximab and methotrexate shows promise in the treatment of thousands of children with a form of chronic arthritis known as polyarticular juvenile idiopathic arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Philadelphia, Pa.
There are many terms used to describe a child with chronic arthritis. These include juvenile rheumatoid arthritis, juvenile chronic arthritis, and juvenile idiopathic arthritis.
There are several types of JIA, all involving chronic joint inflammation. This inflammation begins before children reach the age of 16, may involve one or many joints, and can cause other symptoms such as fevers, rash and/or eye inflammation. Polyarticular JIA affects five or more joints and can begin at any age. Children diagnosed with polyarticular JIA in their teens may actually have the adult form of rheumatoid arthritis at an earlier-than-usual age.
Typically, children with polyarticular JIA receive methotrexate as their first treatment. Researchers recently compared the effectiveness of two different combinations of medications: methotrexate with infliximab (REMICADE®) and a combination of methotrexate, sulfasalazine (Azulfidine®) and hydroxychloroquine (Plaquenil®) versus taking methotrexate alone in very early disease (an average of one month from the diagnosis of JIA).
Researchers looked at 60 patients with polyarticular JIA who ranged in age from four to 16 years old and who had been diagnosed with JIA for less than six months. They were looking to see if patients could reach minimal disease activity ( which was ACR Pedi 75) or remission, at 54 weeks into the study.
Of the 60 patients, 59 completed the study. Out of this 59, 71 percent were considered successfully treated (19 were taking the infliximab and methotrexate combination, 13 were taking the methotrexate, sulfasalazine and hydroxychloroquine combination, and 10 were taking methotrexate alone). Both combinations performed better than methotrexate alone, although the difference was not as pronounced when comparing methotrexate, sulfasalazine and hydroxychloroquine to methotrexate alone. The combination of methotrexate and infliximab produced greater success than the three drug combination.
With regards to disease remission, 68 percent of patients taking infliximab and methotrexate, 40 percent receiving methotrexate, sulfasalazine and hydroxychloroquine and 25 percent receiving methotrexate alone had achieved remission at 54 weeks. Those taking infliximab and methotrexate had been in remission for an average of 26 weeks during the year, which was longer than those on the other medications.
“This study in children is in line with findings in adult rheumatology,” explains Pirjo Tynjälä, MD, PhD, DTM&H; chief pediatrician, Lohja Hospital; researcher, Hosptial of Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland, and lead investigator in the study. “The current target of the treatment in JIA is minimal disease activity and, preferably, remission. When that is the target, in polyarticular JIA, combination therapy with new biologic agents plus methotrexate is more effective than combination therapy with “older” synthetic anti-rheumatic drugs, and clearly more effective than methotrexate alone.”
Patients and their parents should talk to their pediatric rheumatologists to determine their best course of treatment. Dr. Tynjälä also suggests starting drug therapy early – not waiting for the disease to progress without a proper treatment as early, effective drug treatment makes early remission possible.
The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see www.rheumatology.org/annual.
Editor’s Notes: Dr. Tynjälä will present this research during the ACR Annual Scientific Meeting at the Pennsylvania Convention Center at 11:00 AM on Wednesday, October 21 in Room 204 B. Dr. Tynjälä will be available for media questions and briefing at 1:30 PM on Sunday, October 18 in the on-site press conference room, 109 A.
Presentation Number: 2051
Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (A-CUTE-JIA): A Multicenter Randomized Clinical Trial
Pirjo Tynjälä, M, M.D. , Helsinki University Central Hospital, Helsinki, Finland Paula Vähäsalo , Oulu University Hospital Maarit Tarkiainen , Helsinki University Central Hospital, Helsinki, Finland Kristiina Aalto , Helsinki University Central Hospital, Helsinki, Finland Liisa Kröger , Kuopio University Hospital Merja Malin , Tampere University Hospital Anne Putto-Laurila , Turku University Hospital Visa Honkanen , Rheumatism Foundation Hospital, Heinola Pekka Lahdenne , Helsinki University Central Hospital, Helsinki, Finland
Purpose: We compared the efficacy of two combination treatment strategies, methotrexate with infliximab (TNF) and synthetic DMARD combination therapy with methotrexate, sulfasalazine and hydroxychloroquine (COMBO) on methotrexate alone (MTX) in early polyarticular juvenile idiopathic arthritis (JIA). The protocol did not include the use of systemic steroids.
Methods: We performed multicenter randomized clinical trial in 60 patients with polyarticular JIA aged 4-16 years with the duration of JIA less than 6 months. Primary endpoint was American College of Rheumatology Pediatric (ACR Pedi) 75 response at 54 weeks. Secondary endpoints included inactive disease at 54 weeks and the time spent in the state of an inactive disease. Outcome was illustrated by Kaplan-Meier analysis and comparison of therapies was performed by Mantel-Cox test, or Kruskall-Wallis and Dunn's test.
Results: Of the 60 patients, 59 completed the trial (64% females). Twenty-two (37%) had ANA, 13 (22%) were HLA-B27 positive, and one (2%) RF positive. At baseline their mean (± SE) duration of JIA was 0.10 ± 0.02 years, age 9.6 ± 0.4 years, ESR 36 ± 4 mm/hr, active joints 18 ± 1, physician's global 55 ± 2 mm, and CHAQ 0.763 ± 0.082.
Primary endpoint: 42 patients (71%) had ACR Pedi 75 response; 19 (100%) receiving TNF, 13 (65%) COMBO and 10 (50%) MTX (p<0.0001). The difference was significant between TNF and MTX (p<0.0001), and TNF and COMBO (p=0.0005), but not between COMBO and MTX.
Secondary endpoint: At 54 weeks, 13 patients (68%) receiving TNF, 8 (40%) receiving COMBO and 5 (25%) receiving MTX (p=0.002) had inactive state of the disease. Those on TNF reached inactive disease more often than those on MTX (p=0.02), but the response between COMBO and TNF (p=0.050), or COMBO and MTX (p=0.220) was not significant. During the 54-week follow-up, those on TNF spent a mean of 26 weeks (95% CI 18-34) in inactive state of disease. This was longer than those on COMBO (13 weeks, 95% CI 6-20; p=0.044 compared with TNF), or those on MTX (6 weeks, 95% CI 2-10; p=0.001 compared with TNF), but the difference between COMBO and MTX was not statistically significant.
Conclusions: When the target was ACR Pedi 75 response within the first year of therapy in early polyarticular JIA, infliximab plus methotrexate turned out to be superior to synthetic DMARD combination, and even more clearly, superior to MTX monotherapy.
Disclosure: P. Tynjälä, None; P. Vähäsalo, None; M. Tarkiainen, None; K. Aalto, None; L. Kröger, None; M. Malin, None; A. Putto-Laurila, None; V. Honkanen, UCB-Pharma, 3 ; P. Lahdenne, None.
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