Background/Purpose:
Tofacitinib
is an oral Janus kinase inhibitor for the treatment of RA. In a Phase 3 study
(ORAL Start; NCT01039688), tofacitinib monotherapy in MTX-naïve patients
demonstrated significant, durable, and clinically meaningful improvements in RA
signs and symptoms and physical functioning, and inhibition of progression of
structural damage, vs MTX over 24 months.¹
Here, we present a post-hoc analysis of ORAL Start to
assess the efficacy and safety of tofacitinib monotherapy in patients with
early RA or established RA as defined by disease duration.
Interim data have previously been presented.²
Methods: Patients were randomized 2:2:1 to tofacitinib 5 mg twice daily
(BID), tofacitinib 10 mg BID, or MTX (mean MTX dose at end of titration [Month
3], 18.5 mg/week). Clinical efficacy was assessed in cohorts of patients with
disease duration at baseline <1 (early RA) and ≥1 year (established
RA), using ACR20/50/70, Disease Activity Score (DAS)28-4(ESR)<2.6 (DAS28-4[ESR]-remission)
and ≤3.2 (low disease activity), and HAQ-Disability Index (HAQ-DI).
Safety assessments included recording the incidence and severity of all adverse
events (AEs). Results: Although not pre-defined in the original study, a
total of 515 patients had early RA (N=201, N=207, and N=107 for tofacitinib 5
mg BID, tofacitinib 10 mg BID, and MTX, respectively) and 441 patients had established
RA (N=172, N=190, and N=79 for tofacitinib 5 mg BID, tofacitinib 10 mg BID,
and MTX, respectively). For all efficacy parameters at Month 12 and Month 24
within each cohort, response rates and improvements from baseline were
significantly greater (p<0.05) for both tofacitinib doses vs MTX, except for
patients with established RA treated with tofacitinib 5 mg BID (ACR20, ACR50, and
ACR70 at Month 12; change from baseline in HAQ-DI, DAS28-4(ESR)≤3.2, and
DAS28-4(ESR)<2.6 at both Month 12 and Month 24) and tofacitinib 10 mg BID
(DAS28-4(ESR)<2.6 at Month 12). Numerically more tofacitinib-treated patients
with early RA achieved ACR20/ACR50/ACR70 responses, DAS-defined remission and
low disease activity and numerically greater changes from baseline in HAQ-DI at
both Month 12 and Month 24 compared with patients with established RA (Table 1).
Odds ratios for early RA vs established RA were greater than 1 for all efficacy
parameters from Month 1 through Month 24. In general, there was no difference
in AEs or discontinuations due to AEs when patients were sub-grouped by
baseline disease duration. Conclusion:
Tofacitinib monotherapy significantly improved signs and symptoms and physical
function vs MTX in MTX-naïve patients with early (<1 year) and established (≥1 year)
disease. There were generally greater numerical improvements observed in
patients with shorter disease duration. AEs and discontinuations due to AEs
were similar between groups. References:    1.
        Lee EB et al.  N Engl J Med 2014; 370: 2377-2386.

   2.   Huizinga
TWJ et al.  Ann Rheum Dis 2013; 72: 241.