Home > reports from the field > A report from the field: abatacept administered triweekly

A report from the field: abatacept administered triweekly

Sometimes you have those tiny observations from daily clinical practice that are just too short as a message to post to a journal in the field, even in the format of a “letter-to-the-editor” but are also too important not to share with others. These are often the particular case observations rheumatologists share with each other on scientific meetings (i.e. in the meeting area or during dinner, not in the plenary sessions themselevs). These shared reports from the field often form a cnsiderable part of the take home messages when traveling home having attended a scientific meeting. It’s a pity that such practical advice or observations from colleagues although very worthwile are scarce to find upon scientific literature searches. The reason, I guess, is probably that others think the same of an example I will be giving in this blogpost as I do, i.e. the message is too “small” (in number of reported cases and length of content one would share) to send it in to a peer-reviewed scientific journal. As a result, these valuable personal observations of fellow rheumatologists are mainly shared amongst colleagues that are physically met in real lfie, and not shared to a broader audience by using the web. In my opinion blogging such reports from the field could be a very nice way to make also these valuable personal n=1 or n=2 observations from the field avaiiable on internet searching (e.g. Google will for sure pick up this one when someone might type in abatacept triweekly in the near fiture, especially when tags are attached to blog postings). So I would like to make a call to worldwide rheumatologists reading my blog not to hesitate blogging about their own observations from the field too tiny to publish but to relevant not to share (by blogging).

On now for my own first “report from the field” blogpost. It’s about administering abatacept infusions on a triweekly base rather then on standard 4-week intervals. Personally I now have two rheumatoid arthritis (RA) patients that are on triweekly abatacept treatment. Whether that is ideal from a rheumatologist’s point of view remains to be seen, however as far as both patients themselves concern they are very satisfied with their current situation and would rather not change to an other treatment. That’s understandable because before being put on abatacept treatment they of course had conventional DMARDs treatment first (methotrexate, hydroxychloroquine), and also they had failed on anti-TNF treatment. Being e.g. one-and-a-half to two years underway with active rheumatoid arthritis they of course really cherish the moment their inflammatory disease is finally turning into a lower disease activity or even remission picture.

What happened? The first patient, a 57 year old female RA patient, was treated with abatacept according to the standard treatment regimen with infusion of abatecpt every 4 weeks. She had had an active rheumatoid arthritis demanding continuous oral cortcosteroids and the use of methotrexate was being complicated by elevated liver enzymes at higher dosages. Thereafter hydroxychloroquine (Plaquenil) was added to a low dose methotrexate re-challenge and low dose oral corticosteroids. This did not limit her disease activity, and intra-articular injections were sometimes necessary in knee or wrist because of active arthritis. Because of treatment failure she then started golimumab (Simponi) anti-TNF alpha treatment, which she continued to use for four months. Clinically and also in the perception of the patient this did not lower her disease activity at all, also methotrexate was now complicated by hair loss. So in March 2011 methotrexate as well as golimumab were stopped definitely and the patient was prescribed abatacept infusions. Upon having started this treatment she mentioned for the first time that in general her rheumatoid arthritis (that for her also had considerable impact on participation at work) was finally getting less worse. Meanwhile I did however have to give another intra-articular corticosteroid injection in her once again inflamed wrist joint. When she returned on the outpatient clinic (having seen her in between for the wrist injection) she was four months on abatacept every 4 weeks, and she still reported to be quite satisfied, for sure when considering the one-and-a-half year of active RA she had had before. However she told me having had 4 cycles of repeated abatacept infusions that every time all went well for the first three weeks after the infusion followed by a significant flare of the disease in the fourth week.

I decided to do a literature and internet search (PubMed, Google) to look for other physicians reporting the use of abatacept on a triweekly base. I searched extensively and did not find an answer except this slightly related case series report (I thank the authors for sharing!):

Combination Therapy of Abatacept and Anakinra in Children with Refractory Systemic Juvenile Idiopathic Arthritis: A Retrospective Case Series – J Rheumatol January 2011 38(1):180-181; doi:10.3899/jrheum.100726.

In this report one case was described in which a child with juvenile idiopathic arthritis had to be given abatacept on a triweekly base rather then every 4 weeks to prevent two-three times per week recurring fever attacks that remained only in the fourth week after abatacept infusion. In the first three weeks after infusion abatacept prevented such fever episodes that without abatapect would occur every week.

That was all I found upon literature and internet searching. I then contacted the firm that distributes abatacept in the Netherlands, Bristol-Myers Squibb, and they reported not to have had any other doctor asking them how about administering abatacept every 3 weeks instead of every 4 weeks before. They kindly provided me with study (trial) data, and from these data it became clear that (as one can expect in general) there was a considerable variation in abatacept clearance between individual patients. The half-life (t 1/2) of abatacept ranged from 8 to 25 days (mean 13.1 days) in abatacept 10mg/kg body weight trial participants. Thus, whereas one patient (with a t 1/2 of 25 days) still has about the half of the administered abatacept dosage present after 4 weeks, on the other side of the spectrum a patient (with a t 1/2 of only 8 days) could have only one-sixteenth (four half-life episodes) of the administered abatacept dossage left in the body when presenting for the next infusion!

Figure 1. Distributions of predicted steady-state trough serum concentrations by dose group.
(Roy A, et al. J. Clin. Pharmacol.2007;47: 1408–1420)

In other words: when patients are treated with abatacept the remaining active dosage of abatacept in their bodies when presenting for the next infusion after 4 weeks can range from 25-50% (one to two half-life times) to merely 6% (four half-life times) of the infusion dosage that was given four weeks earlier, how about that?

I put her on abatacept triweekly, just saw her back on my outpatient clinic yesterday for the second time since being on a triweekly abatacept regimen. Her rheumatoid arthritis was in remission, she was very satisfied. However she could not do without a very low amount of concomitant oral corticosteroids medication (2.5mg prednisolone once daily), so it was just in balance. But in balance is…in balance 😉

The second patient on a triweekly abatacept dosage regimen has almost the same story, however I hesitated initially because it does not feel good to treat many patients with an unconventional dosing regimen. Also I was worrying whether a “spread-the-word” phenomenon could have influenced patients (e.g. when nurses at the infusion site are talking to patients, asking them how they are, and then mentioning that single patient that is now doing so well on triweekly infusions). However after some hesitation it turned out that also this second patient had really the story of faster-then-average clearance of abatacept, with the typical “three weeks excellent, fourth week bad” story as opposed to abatacept non-responders or partial-respnders that do not notice or report any differences in disease actvty throughout the 4 weeks dosing interval.

Anyway with the remarkable variation of half-life times (8-25 days) and the standard suggested four-week infusion intervals in mind, having some patients (by exception) on a triweekly infusion interval in my opinion isn’t that weird at all. (On the other hand theoretically some patients with prolonged half-life times could possibly do with abatacept infusions on “more then 4 weeks” intervals)

And now you have read this you know..!

B-MS provided me with the following reference for their half-life data:
Roy A, et al. J. Clin. Pharmacol.2007;47: 1408–1420

  1. Joerun
    14 March 2012 at 19:47

    I’m reading your blog from Brazil and I’d like to thank you so much for sharing your experience!

    • 14 March 2012 at 21:56

      Thank you very much, nice to get some feedback, greetings from the Netherlands, Michiel

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