Safety of Anakinra (Interleukin-1 Receptor Antagonist) in Patients Receiving Standard Treatments for Rheumatoid Arthritis: A Large Phase III Study

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Safety of Anakinra (Interleukin-1 Receptor Antagonist) in Patients Receiving

Standard Treatments for Rheumatoid Arthritis: A Large Phase III Study

Category: 17 RA—treatment

Presentation Time: Monday, 3:40 p.m. - 3:45 p.m.

Roy Fleischmann1, Tesser2, Gordon Sun3

1Radiant Research, Dallas, TX;2Protocare, Phoenix, CA;3Amgen, Inc., Thousand

Oaks, CA

Presentation Number: 1541

Keywords: anakinra, IL-1ra, Kineret

To evaluate the safety of anakinra (100 mg/day, subcutaneous injection) for

subjects receiving other standard treatments for RA, data from a large

randomized placebo-controlled international study were reviewed. A total of

1399 subjects were treated for up to 6 months (283 placebo and 1116

anakinra). Entry criteria included: ³3 tender/painful (T/P) and ³3 swollen

joints or morning stiffness³ 45 mins; RA duration³3 months; age³18 years;

DMARDS stable³2 months; corticosteroids/NSAIDs stable³1 months.

Baseline Characteristics: The baseline demographics and disease

characteristics were comparable between placebo and anakinra groups. Subject

median age is 55 years (range 19-85, 23%³65) and 75% are women. Median RA

duration is 7.5 years (range 0.3-60). At baseline 79% of subjects used

DMARDs, 58% corticosteroids, 87% NSAIDs, however, about 11% of subjects did

not use either corticosteroids or DMARDs. Median T/P joint count is 20

(range 0-68) and median swollen joint count is 16 (range 0-66). Median HAQ

is 1.4 (range 0-3) and median CRP is 1.7 mg/dL (range 0.1-25.6).

Infectious Events: Overall, 43.5% placebo subjects and 41.2% anakinra

subjects experienced infectious episodes (serious in 1 [0.4%] placebo

subject and 23 [2.1%] anakinra subjects). None of the serious infections

were fatal and as of 22 November 2000. All but 1 of the serious infections

have been resolved. Infections were reported as severe in 3 placebo subjects

(1.1%) and 37 anakinra subjects (3.3%).

Non-Infectious Events: Serious adverse events were reported similarly in

both treatment groups (7.8% in the placebo and 7.7% in the anakinra).

Adverse events (AE) were reported as severe or greater severity in 13.1%

placebo subjects and 15.5% anakinra subjects. Five of the 1399 treated

subjects died during the 6-month study period (1 [0.4%] placebo subject and

4 [0.4%] anakinra subjects). Nine subjects were diagnosed with malignancies

(5 [1.8%] placebo subjects and 4 [0.4%] anakinra subjects). Injection site

reactions (ISRs) occurred in 32.9% of placebo subjects and 72.6% of anakinra

subjects. ISRs usually occurred for the first time during the first month of

treatment. Most premature study withdrawals due to AE were the result of

ISRs in anakinra subjects (7.1% versus 1.4% in placebo). Worsening of RA was

reported in 27.6% of placebo subjects versus 20.0% in anakinra subjects.

Conclusions: The overall safety profile of anakinra seen in this large phase

III study was consistent with that seen in earlier studies. The only AE

apparently related to anakinra were ISRs. Although a slightly higher

incidence of serious infectious events was reported in anakinra group, the

possibility that anakinra contributed to the development of serious

infections seen in this study cannot be established. This study demonstrated

that anakinra is generally well tolerated for subjects receiving other

standard RA treatments for a broad range of comorbid diseases.