Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor
for the treatment of rheumatoid arthritis (RA). We report tofacitinib
safety, tolerability, and clinical response over 84 months (mo), and radiographic data over 12 mo, in long-term extension (LTE) studies.

Methods: Data were pooled from two open-label studies
(NCT00413699 [ongoing; database unlocked at March 2015 data-cut] and
NCT00661661 [completed]) of patients (pts) with RA
who completed randomized Phase (P)1, P2, or P3 tofacitinib studies. Pts received
tofacitinib 5 or 10 mg BID as monotherapy or
with background DMARDs; data from both doses ±background DMARDs were pooled.
Baseline (BL) was that of P1/P2/P3 studies for pts
enrolling ≤14 days after last dose, and start of LTE study for all
other pts. For radiographic data, BL was last P1/P2/P3 study value. Primary
endpoints: AEs and laboratory safety. Confirmed data are reported for decreased
hemoglobin (Hgb), neutrophil and lymphocyte counts,
and increases >50% from BL in creatinine. Secondary endpoints: ACR
responses, DAS28-4(ESR), HAQ‑DI, and modified total Sharp score (mTSS). Safety data were included over 96 mo and efficacy data up to Mo 84 (n≤30 post-Mo 84).

Results: 4,867 pts were treated (mean [max] duration:
1,107 [2,895] days). BL data were from index studies for 90.9% of
pts. Total tofacitinib exposure was 14,926 pt-years (py); 79.2% of pts maintained initial dose. In total, 2,132 pts (43.8%)
discontinued (AEs: 1,051 [21.6%]; insufficient clinical response: 153 [3.1%]).
Most common AE classes: infections and infestations (67.6%),
musculoskeletal/connective tissue disorders (37.3%), and GI disorders (32.4%).
Most common AEs: nasopharyngitis (18.1%), upper respiratory
tract infection (16.2%), bronchitis (11.7%), and urinary tract infection
(11.5%). Serious AEs occurred in 26.8% of pts
(incidence rate [IR] 9.7/100 py [95% CI 9.2, 10.2]),
and serious infection events (SIEs) in 8.4% of pts
(IR 2.8/100 py [95% CI 2.5, 3.0]). Malignancies
excluding NMSC were reported in 3.0% of pts (IR
1.0/100 py [95% CI 0.8, 1.1]). IRs for SIEs and
malignancies through Mo 96 did not increase vs reported data through Mo 84.¹
Decreased Hgb (>30% decrease from BL/Hgb <8 g/dL) occurred in 6.8%
of pts. Increased aminotransferases (>3 × ULN) occurred in 5.4% (ALT) and
3.1% (AST) of pts. Moderate to severe neutropenia (absolute neutrophil count
[ANC] 0.5–1.5 × 10³/mm³) was noted in 1.5% of pts; there were no confirmed cases of ANC <0.5 × 10³/mm³.
Confirmed absolute lymphocyte counts <0.5 × 10³/mm³
occurred in 1.3% of pts. Increases >50% from BL in creatinine were seen in
2.4% of pts. ACR20, ACR50, and ACR70 response rates were sustained from Mo 1
(73.8%, 49.8%, and 29.3%) to Mo 84 (79.4%, 66.7%, and 46.0%). Mean DAS28‑4(ESR) was 6.29 at BL, 3.74 at Mo 1, and 3.20 at Mo 84. Mean
HAQ-DI score was 1.42 at BL, 0.81 at Mo 1, and 0.78 at Mo 84. Radiographic data
were available for 1,099 pts. Mean mTSS was 24.0 at
BL (last index value), 25.1 at Mo 6, and 24.3 at Mo 12. Mean change from
BL in mTSS was 0.3 at Mo 6 and 0.2 at Mo 12.

Conclusion: Consistent safety and sustained efficacy over
84 mo was seen in pts with RA receiving tofacitinib
5 or 10 mg BID in LTE studies. Changes in mTSS
were minimal at Mo 12 in LTE studies.

Reference: 1. Wollenhaupt
J et al. Arthritis Rheum 2014; 66: S375.