Incidence Of Infusion - Related Reactions
In Patients Receiving Infliximab:
Recommendations For Administration
Guidelines
03/10/05: Abstract presented at EULAR 2004 by Dr Maya Buch
Abstract presented at EULAR 2004
M. H. Buch 1, S. Lindsay 2, D. Bryer 1, A. Fairclough 1,
B. Rees -Evans 1, P. Emery 1
1 Academic Unit of Musculoskeletal Disease, Leeds General Infirmary, Leeds, 2
Remicare Liaison, Schering -Plough Ltd., Hertfordshire, United Kingdom
Background
Infliximab with methotrexate (MTX) is administered for patients with rheumatoid arthritis (RA) (at a dose of 3mg/kg at weeks 0, 2, 6 and then 8 weekly) and for patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA)(at a dose of 5mg/kg weeks 0, 2, 6 and then 6 -weekly).
Objectives
Our aims were to establish i) frequency of infusion-reactions and relation to concomitant treatment and disease ii) timing of reactions and iii) whether any further adverse events developed in the post-infusion monitoring period, enabling guidelines for infliximab and MTX administration to be established.
Methods
As part of our protocol in Leeds infusions 1 -4 are administered over 2 hours and patients monitored for a further 2 hours after completion of the infusion. Infusions 5 –10 are given over 1 hour with 1 hour post -infusion monitoring and infusions 10+ are administered in half an hour with half an hour monitoring. All infusions are administered at the Day Case Unit. Information from all infusions administered to patients receiving infliximab + MTX (+ a small group of patients with RA treated with leflunomide) was retrospectively collected.
Results
A total of 2166 infusions have been administered to a total of 234 patients (208 RA (161 concomitant MTX; 47 concomitant leflunomide), 20 AS (concomitant MTX), 6 PsA (concomitant MTX) (ranging from 2 -28 infusions per person) (age 22-77, 164 female, 69 male, MTX dose 7.5 -25mg weekly). 24 infusions were administered to the patients with seronegative spondyloarthropathy.
Cessation of treatment due to infusion-related anaphylactic reactions was observed in: 6% (n=14) of the whole cohort. This comprised 3% patients in the RA on concomitant MTX (n=5) group, 19% patients in the RA on concomitant leflunomide (n=9) group and none in the seronegative group. All such reactions occurred during infusions 2 -5 except 2% (n=1) of the RA leflunomide group (infusion 6). Another 6% (n=13) of the whole cohort suffered mild reactions. This consisted of 3% (n=4) in the RA on concomitant MTX group, half during infusion 5, the other half during infusions 8 and 10. All continued treatment but with hydrocortisone and chlorpheniramine pre -medication. 6% (n=3) in the RA on concomitant leflunomide suffered mild reactions with 33% (n=1) having to cease treatment, the rest continuing with pre -medication. 20% (n= 4) AS and 33% (n= 2) PsA suffered mild reactions during infusions 2 -5, all continuing with therapy with pre -medication. All occurred within the first 100 mls of infliximab. Other adverse events included pyrexias ranging from 37.2 -38.2 degrees centigrade, systolic pressure<90 mmHg, headaches, nausea. All were self -limiting, all first occurring within the first 4 -5 infusions with a small proportion continuing post induction.
No patients developed adverse events during the post - infusion -monitoring period including those patients receiving shorter infusion times.
12 patients received re -introduction of infliximab after a gap of 13 -16 weeks (following 'ATTRACT' study). None of these patients suffered an infusion reaction or had increased incidence of other adverse events.
Conclusion
The administration of infliximab with concomitant leflunomide in patients with RA conferred increased incidence of infusion -related reactions. Based on the above findings recommendations regarding infliximab administration to patients on MTX should include: i) Greatest care should be taken during the first 5 infusions ii) Infusions 6+ can be administered at a faster rate if no adverse events are observed during the first five iii) The observation post -infusion may not be necessary iv) Stopping and re-starting infliximab does not confer greater toxicity risks