Promising results in a small trial of lupus patients with active polyarthritis1 combined with similar results in several forms of juvenile arthritis and adult-onset Still's disease suggest a therapeutic niche for the interleukin-1 blocker anakinra (KineretR).
In the new trial, four patients with systemic lupus erythematosus (SLE), active polyarthritis, and no other uncontrolled systemic manifestations received 100 mg/day anakinra by subcutaneous self-administration for 3 months. The treatment was safe in all four patients and no drug-related serious adverse events occurred, the study showed. A subjective benefit and a trend toward better activity measures as early as 4 weeks were seen in all patients.
"Because of the good clinical and immunologic response without showing severe side effects, there is considerable potential for anakinra in SLE," lead researcher Benedikt Ostendorf, MD, rheumatologist at the Heinrich-Heine-University Dusseldorf in Germany tells CIAOMed. Additionally, this agent may be useful in patients with mixed connective tissue disease and patients with Still's syndrome, he says.
The study included two males and two females with an average age of 38 years. All had nonerosive polyarthritis refractory to previous treatment, including nonsteroidal anti-inflammatory drugs, antimalarial drugs, steroids, methotrexate, cyclophosphamide, and azathioprine. Disease activity was assessed by number of swollen/tender joints, (European Consensus Lupus Activity Measurement (ECLAM) score, and serologic and immunologic measures.
There were decreases in tender joint count and ECLAM score after 4 weeks, the study showed. After 12 weeks, clinical activity measures tended to increase again, although preliminary results did not provide a detailed explanation for this observation, the authors point out.
During the follow up period, patient 1 remained in remission after discontinuation of anakinra, patient 2 was still receiving anakinra, and patients 3 and 4 discontinued treatment after weeks 34 and 6, respectively, due to arthritic flares.
A niche for IL-1 blockade
Although anakinra has been shown to be relatively ineffective compared to tumor necrosis factor alpha (TNF-α) inhibitors in the treatment of rheumatoid arthritis, evidence suggests that it may be very successfully applied in certain conditions.
"There is a very specific niche that seems to be ideal for anakinra, including pediatric arthritis, adult-onset Still's, and some fairly rare types of conditions including neonatal-onset multi-inflammatory disease (NOMID), also known as Muckle-Wells syndrome," says Phillip Mease, MD, of Seattle Rheumatology Associates in Seattle, Washington. "There are some diseases that appear to be very IL-1 driven, and Still's disease is a beautiful story in that regard," he tells CIAOMed.
Dr. Mease recounts the experience of researchers from Montreal University Hospital who reported on three patients with refractory chronic adult-onset Still's disease requiring high maintenance doses of corticosteroid and immunosuppressive agents. Two of the three patients taking anakinra 100 mg/day became completely asymptomatic after 4 and 5 months, respectively. These findings were presented at the EULAR 2004 meeting in Berlin, Germany.2
"The group in Montreal...showed dramatic benefits quickly all across the board, and it became more clear that there is finally a case where specific IL-1 inhibition may have a very key role," Dr. Mease says, adding that, as a result, many favor starting Still's patients with anakinra.
Anakinra may play an important role in treating refractory systemic-onset juvenile rheumatoid arthritis (SO-JRA) and possibly systemic-onset juvenile idiopathic arthritis. In a study published in the October 2004 issue of the Journal of Rheumatology,3 anakinra treatment resulted in immediate and sustained resolution of symptoms and laboratory markers of inflammation in two patients with SO-JRA. In one case, this improvement occurred after years of failed treatment with other immunosuppressive therapies, the study showed.
Because they have been associated with the development of systemic autoimmune disease, there has been concern about the use of TNF-α inhibitors for SLE. "There is no drug-induced lupus with anakinra, so it is something reasonable to try in patients who have not responded to some of the more traditional therapies," Dr. Mease says. However, he predicts that anakinra will not become a favored treatment for SLE. "It will never gain a foothold because we will see an onslaught of new B-cell directed therapies, which are more targeted to lupus."
References:
- Ostendorf B, Iking-Konert C, Kurz K, Jung G, Sander O, Schneider M. Preliminary results of safety and efficacy of the interleukin 1 receptor antagonist anakinra in patients with severe lupus arthritis. Ann Rheum Dis. 2005;64:630-633.
- Haraoui B, Bourrelle D, Kaminska E. Anakinra in the treatment of adult onset Still's disease. Presented at: EULAR 2004; Berlin, Germany; June 9-12, 2004. Abstract FRI0148.
- Verbsky JW, White AJ. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol. 2004;31:2071-2075.