ACR Congress Review 2019

In the first presentation, the analyses included a total of 1544 tofacitinib (2138.2 patient years) and 7083
bDMARD (9904.9 patient years) initiators. Rates of MACE and serious infection events were similar in
patients starting tofacitinib or bDMARDs for RA. The herpes zoster incidence rate was higher for
tofacitinib versus bDMARDs and hazard ratios (HR) for herpes zoster were significantly increased with
tofacitinib versus bDMARDs (adjusted HR 2.12, 95% CI: 1.22, 3.66). All herpes zoster events were nonserious
with tofacitinib. VTE IRs were similar in both cohorts [2372].
In a second presentation, the authors compared 5-year IRs of malignancy and mortality in a total of 1999
tofacitinib (4505.62 PY) and 6354 bDMARD (16670.84 PY) initiators. RA patients initiating tofacitinib or
bDMARDs had similar rates of total cancer excluding NMSC, NMSC, and death, with adjusted HRs
(95% CI) of 1.04 (0.68, 1.61), 1.02 (0.69, 1.50), and 1.0 (0.62, 1.63), respectively [2874*].
Risk of serious infections with tofacitinib
A poster presenting the comparative incidence rates of serious bacterial, viral or opportunistic infections
in RA patients was presented by Pawar and colleagues. Using data from three US healthcare claims
databases, a total of 123,960 biologic initiators were identified, of which 4.5% were tofacitinib initiators. A
total of 2,958 serious infection events occurred. In the tofacitinib group, the crude IR for serious
infections per 100 person-years ranged from 2.80 (MarketScan) to 7.89 (Medicare). Adjusted HRs
showed higher risk of composite serious infections with tofacitinib compared with abatacept (HR 1.20,
95% CI 1.09-1.31), etanercept (1.27, 1.14-1.42), golimumab (1.35, 1.29-1.40) and tocilizumab (1.46,
1.31-1.63), but similar risk compared to adalimumab, certolizumab and infliximab. Serious bacterial
infection risk was higher in tofacitinib than abatacept (1.15, 1.09-1.21), certolizumab (1.16, 1.10-1.23),
etanercept 1.14 (1.04-1.25) and golimumab (1.21, 1.06-1.39) [2826].
Vinet and colleagues presented results from a study comparing the risk of serious infections in children
born to mothers with chronic inflammatory diseases who used non-TNFi biologics or tofacitinib during
pregnancy, versus unexposed offspring and children exposed to TNFi in utero. The US MarketScan
database was used to identify 16,490 offspring of mothers with RA (4,142), AS (381), PsO/PsA (5,743),
and inflammatory bowel disease (6,731), as well as 164,553 children born to unaffected mothers
matched for age, year of delivery and state of residence. Very few serious infections were detected in
children exposed to non-TNFi biologics or tofacitinib (2 cases [1.9%]: one case was exposed to
tofacitinib, while the other was exposed to abatacept). The percent of serious infections in offspring of
inflammatory disease mothers with no TNFi exposure was 2.1%, while for those with TNFi in utero
exposure, it was 2.3%. In children born to unaffected mothers, the percent of serious infections was
1.6% [1901].
Baricitinib
Post-marketing surveillance of baricitinib safety in RA
A poster presenting baricitinib safety based on post-marketing surveillance data was presented by
Matsuno and colleagues. This interim report summarized registration data including pre-treatment test
rates and AEs. As of August 2018, 1288 patients had been enrolled. Registration data were reported as
follows: women, 81%; mean age, 64 years old; mean RA duration, 12 years; Steinbrocker stage II, 32%;
stage III or IV, 52%; baricitinib 4 mg, 68%; baricitinib 2 mg 32%; MTX use, 57%; corticosteroid use, 51%;
pre-treatment test for tuberculosis, 93%; HBV, 95%; HCV, 93%; and eGFR, 96%. Of 299 AEs collected,
53 were SAEs. SAEs reported in 2 or more patients were pneumonia (n=8), fall (n=4), osteonecrosis
(n=3), herpes zoster (n=2) and interstitial lung disease (n=2). Pulmonary TB (n=1), lymph node TB (n=1)
and DVT (n=1) were also reported as SAEs. Overall, safety findings were consistent with baricitinib’s
known safety profile. These data highlight that care is needed to ensure that all pre-treatment tests are
conducted in all patients [2375].
*Chairman’s Pick