Adalimumab data from real-life study in RA

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Adalimumab data from real-life study in RA

Rheumawire

June 17, 2004 Nainggolan

Berlin, Germany - Initial results from the Research in Active RA:

Adalimumab Trial (Humira®) (ReACT) with adalimumab in patients with

rheumatoid arthritis (RA) were announced with much fanfare by its

manufacturer, Abbott Pharmaceuticals, at last week's EULAR 2004 meeting.

But some doctors there said they thought the trial was just a " marketing

exercise " and a " seeder study " to try to get patients onto the drug,

which is the third TNF blocker to be approved after etanercept (Enbrel®,

Amgen/Wyeth) and infliximab (Remicade®, Centocor). To date, adalimumab

has been approved in 41 countriesincluding the all-important US and EU

marketsand launched in 26.

However, Dr Gerd Burmester (Universitatsklinikum Charite, Berlin,

Germany)who presented some of the ReACT datamaintained that ReACT " is

important, because " it's a 'real-life' study, and it's different from a

clinical trial. "

ReAct is the largest anti-TNF trial to be conducted in Europe and has so

far recruited more than 6000 patients with moderate to severe RA, who

are being treated with adalimumab 40 mg every other week in addition to

their existing therapies.

Results from the first 2008 patientsreported as 3 separate abstracts

[1,2, 3]showed that 24% achieved clinical remission within 3 months

(defined by Disease Activity Score <2.6), 42% of patients responded

favorably to adalimumab within 2 weeks of the first dose, and the safety

profile of the drug was similar to that seen in previous studies.

" The data on safety and efficacy from such a large trial confirm the

favorable outcomes seen in the initial Humira pivotal trials in RA, "

Burmester noted.

The ReAct data also demonstrated that adalimumab can be successfully

" added on " to other disease-modifying antirheumatic drugs (DMARDs).

Adalimumab showed similar efficacy whether combined with 1, 2, or more

concomitant DMARDs (no additional efficacy was seen when it was added to

more than 1 DMARD, however). And those taking the new TNF blocker with a

concomitant DMARD showed slightly better responses than those taking it

alone.

In addition, adalimumab showed efficacy in patients who had previous

experience of other biologic drugs in the ReACT study. These were not

the only data on this subject, either. Several presentations and posters

discussed the safety and efficacy of adalimumab after other anti-TNF

agents or the interleukin-1 antagonist anakinra (Kineret®, Amgen).

The largest of these was a report on 396 patients included in the

Swedish nationwide follow-up system for biologics [4] by Dr N Feltelius

(Swedish Medical Product Agency, Uppsala). Nearly half the patients

switched to adalimumab due to loss of efficacy on a previous biologic,

and most of the remainder did so because of adverse reactions. Data on

treatment efficacy were available for 294 patients.

" The switch from etanercept or infliximab to adalimumab seems safe, "

commented Feltelius, adding, " Recurrence of a previous adverse reaction

was rare. " A treatment response was achieved in almost two thirds of the

patients, he noted, but outcomes for individual patients " need further

analysis, " he concluded.

In another presentation [5], Dr P Vela (Reumatologia Hospital General

Alicante, Spain) and colleagues described outcomes in around 100 RA

patients who had failed a first biological treatment. They found that

most patients who do not respond well to a first biologic have a good

chance of success with a second. However, there was also a group of

" nonresponders' " in their case around 25% of patientswho do not seem to

respond to any biologic therapy, Vela noted, adding, " Today we do not

have a good solution for these patients. "

Results with adalimumab in other indications were also reported at

EULAR. However, these were very small trials, and it is still very early

days for this drug in psoriatic arthritis (PsA), ankylosing spondylitis

(AS), and sciatica. Both etanercept and infliximab have shown benefit in

PsA and AS, so Abbott will be hoping that adalimumab can mirror this

success.

In the PsA study, reported by Dr C Ritchlin (University of Rochester,

NY), treatment with one 40-mg dose of adalimumab resulted in significant

improvement in the signs and symptoms of PsA in 15 patients [6].

And in the AS study, Dr H Haibel (Universitatsklinikum Charite, Berlin,

Germany) said adalimumab every other week for 12 weeks showed

significant improvement of spinal symptoms in active AS in 10 patients

[7].

Finally, a pilot study of adalimumab in sciatica suggested a possible

benefit of the drug in reducing leg pain and back-related disability in

9 patients [8]. As previously reported by rheumawire, another pilot

study has shown that a single dose of infliximab produced long-term

relief of sciatica pain.

Sources

Burmester GR, Monteagudo Saez I, Malaise M, et al.

Efficacy and safety of adalimumab (Humira®) in European clinical

practice: The ReAct trial. Presented at: EULAR 2004; Berlin, Germany;

June 9-12, 2004. Abstract OP0105.

Bombardieri S, Moutsopoulos HM, McKenna F, et al.

Rapid response to adalimumab (Humira®) after first dose: the ReACT

trial. Presented at: EULAR 2004; Berlin, Germany; June 9-12, 2004.

Abstract FRI0042.

Mariette X, Bijlsma JWJ, Herold M, et al. Efficacy

evaluation of adalimumab (Humira®) in combination with single and

multiple disease-modifying anti-rheumatic drugs in the ReAct trial.

Presented at: EULAR 2004; Berlin, Germany; June 9-12, 2004. Abstract

FRI0099.

Feltelius N, Fored M, Blomqvist P, et al. Safety and

efficacy of adalimumab in arthritis patients previously treated with

another biologic agent. Presented at: EULAR 2004; Berlin, Germany; June

9-12, 2004. Abstract FRI0180.

Vela P, Pascual E, Pedraz T, et al. Outcome of

rheumatoid arthritis patients who failed to a first biological

treatment. Presented at: EULAR 2004; Berlin, Germany; June 9-12, 2004.

Abstract FRI0161.

Ritchlin C, Anandarajaha A, Totterman S, et al.

Preliminary data from a study of adalimumab in the treatment of

psoriatic arthritis. Presented at: EULAR 2004; Berlin, Germany; June

9-12, 2004. Abstract SAT0054.

Haibel H, Brandt C, Rudwaleit M, et al. Preliminary

results of an open-label, 12-week trial of adalimumab in the treatment

of active ankylosing spondylitis. Presented at: EULAR 2004; Berlin,

Germany; June 9-12, 2004. Abstract SAT0040.

Brennan S, Vanharanta H, Keenan A, et al. Treating

sciatica with adalimumab: a pilot study. Presented at: EULAR 2004;

Berlin, Germany; June 9-12, 2004. Abstract SAT0146.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org