Adult Drug Improves Function in Patients with a Ra

Newswise — Anakinra (Kineret), a medication used in the treatment of rheumatoid arthritis in adults, improves physical function in children and young adults with neonatal-onset multisystem inflammatory disease, and may provide a clue about what causes these types of diseases, according to research presented this week at the American College of Rheumatology's Annual Scientific Meeting in Boston, Mass.

NOMID is a rare disorder that is caused by oversecretion of a protein called interleukin (IL)-1? that leads to inflammation in numerous organs in the body. NOMID is often discovered between birth and six weeks of age when newborns develop an unusual rash. Other symptoms include fever, aseptic meningitis, swelling of the optic nerves, joint pain and deformity—particularly in the knees, hearing and sight loss, mental disability, and stunted growth.

Researchers studied 18 patients between the ages of four and 28 to determine the functional outcomes of one year of treatment with anakinra. Participants received daily injections of anakinra while functional outcomes such as joint range-of-motion, pain, walking and running, motor and process skills, IQ, and disability were monitored.

After 12 months of treatment with anakinra, improvement in functional motor performance and reduction of pain and disability were seen using standardized measurements.

However, the absence of improvement in IQ and other more cognitively related scores suggests that, although motor disability may be partially reversible with the use of anakinra, the drug does lead to improvement in every aspect of the disease.

"We have shown that anakinra treatment has resulted in measurable improvement in daily life function (mobility and self care)," said investigators in the study, Scott M. Paul, MD; physiatrist; rehabilitation medicine department, National Institutes of Health, Clinical Center and Raphaela Goldbach-Mansky, MD, MHS, staff clinician and principal investigator; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health. "It has been most rewarding to actually see the impact on the subjects' daily lives, most strikingly demonstrated by some of the subjects who were unable to walk and now can—some even without the assistance of a cane or walker."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, http://www.rheumatology.org/annual.

Editor's Notes: Dr. Paul will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 2:30 " 4:00 pm EST on Thursday, November 8, 2007, in Room 253. Presentation Number: 678

Functional Outcomes of One Year of Treatment of Neonatal Onset Multisystem Inflammatory Disease (NOMID) with Anakinra

Scott M. Paul, Hanna Hildenbrand, Minal S. Jain, Michaele R. Smith, Edith Wiggs, Leora Comis, Delores Koziol, Raphaela Goldbach-Mansky. National Institutes of Health, Bethesda, MD

Objective: To determine the functional outcomes of 1 year of treatment with the recombinant interleukin-1 receptor antagonist anakinra of patients with NOMID, an auto-inflammatory syndrome caused by mutations in CIAS1, a gene associated with up-regulation of IL-1? production.

Methods: An open label prospective treatment trial of 18 subjects between 4 to 28 years was performed. Subjects received daily subcutaneous injection of anakinra starting at 1mg/kg/day, increasing to 3.5 mg/kg/day if symptoms persisted. Functional outcome measures including joint range of motion (ROM), 100mm visual analogue scale of pain (PainVAS), the 9 minute walk-run test (9MW), the Assessment of Motor and Process Skills (AMPS), the Pediatric Evaluation of Disability Inventory (PEDI), and standard IQ testing were obtained at baseline and 12 months.

Results: The mean joint ROM z-score (derived by averaging z-scores of ROM in all measured joints) improved from 0.15 to 0.61 (approaching significance, p=0.07). PainVAS decreased from 40 to 7.9 (p<0.001). At baseline, the ambulatory subjects performed below the 5th percentile for their age on 9MW. After 12 months of treatment, there was a trend towards improved endurance, with an increase of 14% in the ratio of observed value and 5th percentile for age (p=0.17). Mean AMPS z-scores were below age matched norms at baseline and 12 months. However, AMPS motor z-score improved from -3.15 to -0.97 (p=0.007); mean improvement in AMPS process z-score, from -1.05 to -0.08, was not significant. Mean PEDI scaled scores were below normal at baseline and 12 months, but there was improvement in the mobility domain of 6.5 (p=0.012). Mean IQ was in the mild mental retardation range at baseline and did not change after 12 months of treatment.

Conclusions: Improvement in the functional performance and reduction in disability were demonstrated after 12 months of treatment with anakinra. The concomitant decrease in pain and strong trend towards improvement in range of motion may provide the physiological bases for the observed improvement in function under treatment. The absence of improvement in IQ, AMPS process z-score, PEDI social and self-care scaled scores suggest that, although motor disability is partially reversible, CNS deficits may be more permanent.

Disclosure Block: S.M. Paul, None; H. Hildenbrand, None; M.S. Jain, None; M.R. Smith, None; E. Wiggs, None; L. Comis, None; D. Koziol, None; R. Goldbach-Mansky, None.