Tofacitinib effective in East Asian patients with moderate to severe psoriasis
The oral Janus kinase inhibitor tofacitinib demonstrates superior efficacy vs placebo after 16 weeks of treatment in Asian patients with moderate to severe psoriasis, according to the results of a phase III trial. Furthermore, the improvements may be sustained up to week 52, with no unexpected safety findings.
A total of 266 patients (mean age 41.1 years; 72.9 percent male; mean body mass index, 25.3 kg/m2) from China, Taiwan and Korea were randomly assigned to treatment groups receiving tofacitinib 5 mg (n=88), 10 mg (n=90), placebo (n=88) twice daily for 52 weeks. Placebo-treated patients advanced to tofacitinib at week 16.
At week 16, the primary endpoints of proportion of patients achieving Physician’s Global Assessment (PGA) response (‘clear’ or ‘almost clear’) and proportion of those achieving ≥75 percent reduction from baseline Psoriasis Area and Severity Index (PASI75) was greater in both tofacitinib 5 and 10 mg treatment arms than in the placebo arm (PGA: 52.3 and 75.6 percent vs 19.3 percent, respectively; PASI75: 54.6 and 81.1 percent vs 12.5 percent, respectively; p<0.0001 for all). [J Dermatol Sci 2017;doi:10.1016/j.jdermsci.2017.05.004]
Of the tofacitinib 5 and 10 mg responders, 73.6 and 75.0 percent maintained PGA response and 76.8 and 84.9 percent maintained PASI75 up to week 52, respectively.
Over 52 weeks, serious adverse events (AEs) were reported in 2.2 to 4.5 percent of patients across treatment groups, with adverse events leading to treatment discontinuation in 1.1 to 6.8 percent.
“East Asian patients with psoriasis represent a distinct population and have demonstrated differences in disease activity and treatment outcomes compared with other regions. Therefore, it is important to examine the efficacy and safety of potential psoriasis therapies specifically in these patients,” the investigators said. [G Ital Dermatol Venereol 2016;151:412–431]
“Although no direct comparisons can be made, generally higher PGA and PASI75 response rates were observed with tofacitinib 5 mg and 10 mg [twice daily] compared with the same doses in global psoriasis studies,” they continued. [Lancet 2015;386: 552–561; Br J Dermatol 2015;172:1395–1406; 173:949–961; J Am Acad Dermatol 2016;74:841–850]
The higher response rates observed in East Asian populations may be attributed to differences in patient characteristics, including lower body weight, shorter disease duration, less prior use of biologic therapies and higher baseline disease severity compared with global clinical study populations, they explained. [J Dermatol 2016;43:869–880]
“The overall safety profile of tofacitinib in this study was [also] generally consistent with that observed in the global studies,” they added.
The study had several limitations, including the lack of placebo arm beyond week 16 and the lack of any active comparator control arm throughout the study, the relatively limited sample size and timeframe that prevented the accurate assessment of the frequency of rare or uncommon AEs or those with long latency (eg, malignancy or cardiovascular AEs).
“As this was not a head-to-head study comparing efficacy between global and East Asian patients, no formal statistical comparisons were made and therefore only general indirect observations are possible. Finally, it is unclear how applicable the results from this study are to East Asian patients living outside the region,” the investigators said.
In an email to MIMS, Dr Benson Yeo from the National Skin Centre in Singapore and who was not involved in the study, commented that the present data provide tailored information to doctors who treat East Asians with psoriasis on a regular basis.
“The primary endpoints used in the study [the proportion of patients achieving a PGA response of ‘clear’ or ‘almost clear’, and the proportion of patients achieving PASI 75 response] are consistent with the current benchmark of most clinical trials of psoriasis and are stringent criteria which corresponds to significant clinical improvement,” Dr Yeo noted.
He pointed out that tofacitinib as an oral medication is a welcome addition to the armamentarium in psoriasis therapy where treatment failure still occurs due to factors such as poor response, poor tolerability, costs or patient preference for administration route.
“Clinicians planning to use tofacitinib should, however, remain cognizant of the possible adverse events, including upper respiratory tract infection, nasopharyngitis, herpes zoster and hyperlipidaemia,” Dr Yeo said. “Furthermore, [evaluating] rarer adverse events with longer latency period, such as malignancies and cardiovascular adverse events, would require a larger sample size, extension studies and postmarket surveillance.”