Atreat-to-target strategy for manag- ing patients with axial spondyloar- thritis failed to meet its primary efficacy endpoint but still showedseveral suggestive indications of benefitcompared with usual care in a multicentre,randomised study with 160 patients.
The treat-to-target management strategytested in the Tight Control in Spondyloarthritis (TICOSPA) studyaimed to get patientsto an AnkylosingSpondylitis DiseaseActivity Score (ASDAS) of less than2. 1, as recommendedfor patients with axial spondyloarthritis(axSpA) by an international task force(Ann Rheum Dis. 2018 Jan;77[ 1]: 3-17). Alsonotable about the study was its primaryendpoint, at least a 30% improvement in theAssessment of Spondyloarthritis International Society Health Index (ASAS HI) (ClinExp Rheumatol. 2014 Sep-Oct;32[ 5, Suppl85]:S-105-8), a measure of health-relatedquality-of-life that the study organisers selected in part because of its distinction fromthe treatment target.
“For the first time in rheumatology, wetargeted inflammation to have an impacton another domain of the disease. Despitenot reaching statistical significance, wesee a difference between the groups,” Dr.Anna Moltó said at the congress.
After 12 months in the study, the 80 axSpA patients assigned to the treat-to-target regimen had a 47% rate of attainmentof the primary endpoint, compared with36% of the 80 patients assigned to usualcare, an 11% absolute between-groupdifference with a P value that came closeto but failed to achieve the conventionalstandard of statistical significance afteradjustment for potential confounders (P= .09). Six secondary outcomes showedstatistically significant improvements compared with the control patients, includingASAS 40. Five additional metrics showednominal between-group improvementswith the treat-to-target strategy that werenot statistically significant, including various forms of the ASDAS.
One additional notable finding camefrom a cost-efficacy analysis run by Dr.Moltó and associates, which showed thatthe treat-to-target strategy was “dominant” over usual care by producing bothbetter outcomes as well as a lower totalcost, compared with control patients,even though twice as many patients onthe treat-to-target strategy received abiologic disease-modifying antirheumaticdrug (bDMARD) compared with patientsin the usual care group. The incrementalcost utility ratio for treat-to-target was
19,430 euros per quality-adjusted life-yeargained, putting the strategy into the rangeof a “cost-effective” approach, and thetwo treatment arms also had comparablesafety, said Dr. Moltó, a rheumatologist atCochin Hospital in Paris.
The 11% increase in treat-to-targetpatients achieving at least a 30% improvement in their ASAS HI score “is potentiallyclinically relevant” because the comparator arm in the study received “very active”usual care and was not by any measurea true placebo control group, noted Prof.Maxime Dougados, a rheumatologist andprofessor of medicine at Cochin Hospitaland senior investigator for the study. Ingeneral, in treatment studies of rheumatologic diseases a 10% or greater absoluteincrease in the incidence of a beneficialoutcome is considered clinically meaningful when compared with an actively treated control arm, he noted.
“Using the ASAS HI score was very am-
bitious for the study, and it’s a very relevant
outcome,” said Dr. Sofia Ramiro, a rheuma-
tologist at Leiden (Netherlands) University
Medical Centre who was not associated
with the study and chaired the session
where Dr. Moltó gave her report. “We have
had treat-to-target trials that showed bene-
fit when disease activity was the endpoint.”
But when a study “targets treatment to
[reducing] disease activity and then uses dis-
ease activity as the
you expect to see an
effect, but it is circu-
lar reasoning and we
are left with chal-
lenges in interpreting
the results. Now
we have a trial that
is formally [neutral]
but with a different,
more ambitious end-
point. All the indications are for benefit from
treat-to-target for both the primary endpoint
and for all the other endpoints.”
“We were in a difficult situation when
choosing the outcome. We didn’t know
whether a 30% improvement in the ASAS
HI was really relevant, but it seems to
be,” said Prof. Désirée van der Heijde, a
rheumatologist and professor of medi-
cine at Leiden University Medical Centre
and a collaborator on Dr. Moltó’s study.
“I’d choose ASAS HI again as a primary
endpoint” for a treat-to-target study in
patients with axSpA, she said, but added
that a 30% improvement in this score
as the response threshold may warrant
reconsideration. Both Prof. van der Heijde
and Prof. Dougados agreed that at least
one additional study with a somewhat
similar design is needed to better docu-
ment and confirm a role for a treat-to-tar-
get strategy in axSpA patients.
The TICOSPA study ran at 10 Frenchcentres and 4 centres each in Belgium andthe Netherlands. The study enroled adultswith rheumatologist-diagnosed axSpAwith an ASDAS score greater than 2. 1 whohad not yet received a bDMARD, had notyet maxed out on their dosage of NSAIDs,and had certain baseline immunologic and
TICOSPA: Efficacy of treat-to-target strategy
suggested in axial spondyloarthritis
DR. MOLTÓ PROF. VAN DER
PROF. DOUGADOS DR. RAMIRO
Continued on page 9