|Year : 2019 | Volume
| Issue : 4 | Page : 205-208
Efficacy of tofacitinib in patients with moderate-to-severe psoriasis who had inadequate responses to prior biologics
Yi-Wei Huang1, Tsen-Fang Tsai2
1 Department of Education, National Taiwan University Hospital, Taipei, Taiwan
2 Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
|Date of Submission||11-Nov-2018|
|Date of Decision||24-Dec-2018|
|Date of Acceptance||04-Jan-2019|
|Date of Web Publication||16-Dec-2019|
Dr. Tsen-Fang Tsai
Department of Dermatology, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei
Source of Support: None, Conflict of Interest: None
This retrospective observational study examined the effect of tofacitinib in two Phase 3 controlled studies. Patients (n = 15) were randomized to receive either tofacitinib 5 or 10 mg or placebo, twice daily. Most patients in both groups were responsive to tofacitinib at week 16. Four patients (25%) used two or more biological agents before tofacitinib. Two of these refractory patients demonstrated a response. In conclusion, tofacitinib provides a comparable therapeutic effect in both prior biologics responders and nonresponders during the initial 16 weeks, especially those exposed to etanercept. Tofacitinib remains a treatment choice in refractory patients who failed multiple previous biologics.
Keywords: Biologic failure, Chinese, psoriasis, switch, tofacitinib
|How to cite this article:|
Huang YW, Tsai TF. Efficacy of tofacitinib in patients with moderate-to-severe psoriasis who had inadequate responses to prior biologics. Dermatol Sin 2019;37:205-8
|How to cite this URL:|
Huang YW, Tsai TF. Efficacy of tofacitinib in patients with moderate-to-severe psoriasis who had inadequate responses to prior biologics. Dermatol Sin [serial online] 2019 [cited 2020 Jan 29];37:205-8. Available from: http://www.dermsinica.org/text.asp?2019/37/4/205/273098
| Introduction|| |
Tofacitinib is an oral Janus kinase inhibitor which has comparable efficacy to etanercept in psoriasis. A previous study has shown high efficacy of tofacitinib in Asian psoriasis patients. In this study, we report the efficacy of tofacitinib in patients with moderate-to-severe psoriasis who failed prior biologics.
| Methods|| |
This retrospective observational study included patients with moderate-to-severe psoriasis, defined as baseline Psoriasis Area and Severity Index (PASI) at least 12% and body surface area 10%, in two Phase 3 controlled studies (NCT01276639, NCT01815424). The study was approved by National Taiwan University Hospital (IRB No. 201012013MA obtained on Jan 17, 2011 and 20130607MSD obtained on Aug 2, 2013). Written informed consent was obtained from all participating individuals. The detailed protocol has been reported previously. Briefly, all patients were randomized to receive either tofacitinib 5 or 10 mg or placebo, twice daily till week 16, followed by extension up to more than 4 years. All PASI data were assessed by the same physician for both tofacitinib and prior biologics.
| Results|| |
All 45 patients received at least one systemic treatment before tofacitinib. A total number of 15 patients were previously treated with biological agent (s) for more than 16 weeks [Figure 1]. Etanercept was the most (69%) commonly used biologics. Four participants had tried more than one biologics.
|Figure 1: The algorithm demonstrates the treatments and the numbers of patients achieving PASI 75 in each group|
Click here to view
Biologics responder group (47%) is defined as patients achieving ≥75% reduction in PASI (PASI 75). Among these seven participants, four (57%) reached PASI 75 at week 16 after tofacitinib usage. All three patients taking 10 mg tofacitinib reached PASI 100 response at week 16. At week 52, the ratio of patients reaching PASI 75 remained the same despite dosage change for the placebo group.
Among the eight patients (53%) who responded poorly to previous biologics, five (63%) achieved PASI 75 at week 16 after tofacitinib initiation. However, only two maintained therapeutic effect until week 52.
Six patients joined extension study, receiving tofacitinib 10 mg twice daily up to 4 years. One of them dropped out at 24 months with PASI improving from 33.7 to 8.8. Another case showed dramatic improvement and reached PASI 100 with an early extension at week 12 of the prior tofacitinib trial. The other patient achieved and remained PASI 75 throughout the extension period. The other three patients did not reach PASI 75 at month 48, while two of them were responsive to tofacitinib at week 52.
| Discussion|| |
Prior biologic inadequate response negatively affects the subsequent biologic response.,,,, The definition of prior inadequate response was vague without exact PASI score provided. In our case series, we reported treatment efficacy of tofacitinib after failure of prior biologics, and the prior PASI response was also provided. Most patients in both groups were responsive to tofacitinib in the initial 4 months. Patients in biologics failure group demonstrated a higher respond rate (63%) at week 16 to tofacitinib, either 5 mg or 10 mg twice daily. However, 57% of patients in biologics responder group reached PASI 75 at week 52 compared to 25% in biologic failure group.
The economic burden for relief of psoriasis symptoms is substantial., Cost-effectiveness of different targeted drugs as an initial therapy has been examined; however, tofacitinib was not assessed. As the patent expiration of tofacitinib is approaching and significant price falling is already happening in some countries, such as in China and India, the role of tofacitinib in psoriasis treatment deserves reevaluation. For the reason that the willingness to pay threshold of Taiwanese psoriasis patients is strongly related to the influence of social activities, patients experiencing less impacts on personal relationships are more likely gain advantages from tofacitinib nowadays. Our study demonstrated that four cases [cases 4, 5, 6, and 7 in [Table 1] responded to tofacitinib remarkably and earlier. Cases 5, 6, and 7 achieved PASI 100, PASI 99, PASI 100 respectively, at week 8, while PASI was 1.2 for case 4 at week 12. The erythema, induration, and scaling of lesions of cases four and seven improved dramatically after the first administration. Our findings revealed a potential cost-effective feature of tofacitinib to selected patients with prompt improvement. Future studies should concentrate on selecting candidates for tofacitinib timely to provide cost-effective treatment. Yet, to provide the better evidence-based recommendation, more investigations are needed to estimate the cost of treatment of tofacitinib versus other biologics after failure of prior biologics.
|Table 1: Demographics, treatments and PASI scores of the patients who receive tofacitinib after previous biologics.|
Click here to view
Psoriasis is a chronic inflammatory process that requires continuous treatment. In our study, six patients joined extension trial and two-thirds of them demonstrated loss of therapeutic effect. In patients who lost tofacitinib response at week 52, three entered extension trial at week 28 due to insufficient clinical response. Yet, the dose of tofacitinib (10 mg BID), which was later unblinded, remained unchanged for them. One reached PASI 75 as soon as week 8, but PASI fluctuated between 1.2 and 15.5 throughout the entire trial period. The other reached PASI 75 at week 16 with fluctuation of disease (PASI 3.9–43.9). The last patient reached PASI 75 at week 76 and the best response was seen at week 113 with PASI 4.6. Notably, episodes of upper respiratory infection were recorded concurrently with clinical worsening in all these three patients.
Patients who failed more than one prior biologics showed less improvement at week 52. Four patients (25%) used two or more biological agents before tofacitinib, while three of them failed more than one. Two (50%) of these refractory patients demonstrated response to tofacitinib. One of them reached PASI 75 at week 16, but his psoriasis worsened at week 52. The other patient reached PASI 75 with the use of etanercept and ustekinumab but failed with adalimumab. Gradual improvement was seen with tofacitinib 5 mg BID, and PASI 75 was reached at week 52.
| Conclusion|| |
Tofacitinib remains a treatment option in psoriasis patients who failed multiple previous biologics and showed comparable therapeutic effect in both prior biologics responders and nonresponders during the initial 16 weeks, especially those exposed to etanercept. However, our study is limited by small case number, heterogeneous prior treatments, and the fact that etanercept was the most commonly used biologics. Different biologics have recently been developed through diverse mechanisms of actions, and many of them demonstrate improved therapeutic effect. Further research should be performed to determine the potential role of tofacitinib as a therapeutic option after prior biologics failure.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest
| References|| |
Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al.
Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: A phase 3 randomised non-inferiority trial. Lancet 2015;386:552-61.
Zhang J, Tsai TF, Lee MG, Zheng M, Wang G, Jin H, et al.
The efficacy and safety of tofacitinib in asian patients with moderate to severe chronic plaque psoriasis: A phase 3, randomized, double-blind, placebo-controlled study. J Dermatol Sci 2017;88:36-45.
Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, et al.
Tofacitinib, an oral janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Results from two randomized, placebo-controlled, phase III trials. Br J Dermatol 2015;173:949-61.
Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, et al.
Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N
Engl J Med 2010;362:118-28.
Kerdel F, Zaiac M. An evolution in switching therapy for psoriasis patients who fail to meet treatment goals. Dermatol Ther 2015;28:390-403.
Wang TC, Hsien YC, Wang TS, Tsai TF. Practical experience of ustekinumab in patients with moderate-to-severe psoriasis who had inadequate therapeutic response to prior tumor necrosis factor blockers. Dermatol Sin 2015;33:5-10.
Wang TS, Tsai TF. Safety and effectiveness of adalimumab in patients with moderate-to-severe psoriasis who had inadequate therapeutic response to prior etanercept: A case series in Taiwan. Dermatol Sin 2013;31:11-8.
Wang TS, Chan CC, Chiu HY, Tsai TF. Secukinumab in psoriasis patients with prior ustekinumab treatment: Results of a single-center experience. Dermatol Sin 2017;35:25-9.
Brezinski EA, Dhillon JS, Armstrong AW. Economic burden of psoriasis in the United States: A systematic review. JAMA Dermatol 2015;151:651-8.
Chen KC, Hung ST, Yang CW, Tsai TF, Tang CH. The economic burden of psoriatic diseases in Taiwan. J Dermatol Sci 2014;75:183-9.
Hendrix N, Ollendorf DA, Chapman RH, Loos A, Liu S, Kumar V, et al.
Cost-effectiveness of targeted pharmacotherapy for moderate to severe plaque psoriasis. J Manag Care Spec Pharm 2018;24:1210-7.
Ko WC, Tsai TF, Tang CH. Health state utility, willingness to pay, and quality of life among Taiwanese patients with psoriasis. Dermatol Sin 2016;34:185-91.