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Pityriasis lichenoides chronica induced by adalimumab in a patient with psoriasis with response to methotrexate
3465 Pityriasis lichenoides chronica induced by adalimumab in a patient with psoriasis with response to methotrexate Carmen Martinez Peinado, Complejo Hospitalario de Jaen, Jaen, Spain; Paloma Nogueras Morillas, Hospital Universitario Virgen de las Nieves, Granada, Spain; Cristina Garrido Colmenero, Hospital Universitario Virgen de las Nieves, Granada, Spain; Antonio Gallego Torres, Hospital Comarcal San Agustin de Linares, Jaen, Spain; Manuel Galan Gutierrez, Complejo Hospitalario de Jaen, Jaen, Spain; Ignacio Valenzuela Salas, Hospital Valle de los Pedroches, Pozoblanco, Cordoba, Spain; Ricardo Ruiz Villaverde, Hospital Universitario Virgen de las Nieves, Granada, Spain; Rocio Solorzano Mariscal, Complejo Hospitalario de Jaen, Jaen, Spain Introduction: Tumor necrosis factor alpha (TNF-a) inhibitors have been demonstrated to be effective in treating immunomediated inflammatory diseases, such as psoriasis, rheumatoid arthritis and inflammatory bowel disease. However, these biologicals may induce infections, neoplasms, or autoimmune diseases. Cutaneous side effects have been reported, including dermatitis, psoriasis-like rash, vasculitis, keratosis follicularis, dermatitis herpetiformis, alopecia, folliculitis, perniosis-like eruptions, granuloma annulare and sarcoidosis. Until now, there is only one reports describing the appearance of pityriasis lichenoides chronica (PLC) in association with adalimumab treatment in a patient with severe psoriasis. We report the first cases of pityriasis lichenoides chronica (PLC) developed while on adalimumab and successfully treated with methotrexate.
than a quarter of placebo-treated patients with a PASI50 response achieved a PASI90 response. Younger age, male gender, and lower weight were associated with a greater chance of achieving PASI90 with adalimumab. Design, study conduct, and financial support for the study were provided by AbbVie; AbbVie participated in the interpretation of data, review, and approval of the abstract; all authors contributed to the development of the publication.
Case report: A 45-year-old man hypertensive, diabetic and no drug allergies, with a history of severe, recalcitrant psoriasis for which he received biologic treatments (ustekinumab and etanercept) without control of the disease. He started adalimumab and within the second month, there was significant clinical improvement. However, 10 weeks after commencing treatment, he developed new cutaneous lesions consisting of erythematous papules, with central scaling, affecting the trunk, the buttocks, and extremities, sparing the face, palms, and soles. These were asymptomatic and did not coincide with intercurrent illness or other new pharmacologic therapy. Microscopic examination of a skin biopsy showed findings consistent with PLC. No clonal rearrangement of the TCR was detected. It was decided, on the assumption of a synergistic action, to start methotrexate (MTX) therapy (15 mg/week) and adalimumab was continued because of the severity of psoriasis. Complete remission was achieved in 6 weeks with residual pigmentation and bowel disease was controlled. This was discontinued but 15 days later PLC recurred and MTX was again introduced and led to new remission. Discussion: The pathogenesis of PLC is not well understood. However, CD4+ T helper cells are heavily implicated, and alterations in T-cell function and cytokine production, secondary to TNF inhibition, may be responsible for triggering the disease. The treatment of PLC relies on antibiotics and/or phototherapy. In case of failure, immunosuppressants are recommended. The course of PLC is variable, spontaneous regression is possible. MTX is effective for PLC, and represents an interesting therapeutic option because of the synergistic action of MTX and TNF-a inhibitors in psoriasis. Commercial support: None identified.
2571 Predicting PASI90 response among adalimumab-treated patients with moderate to severe psoriasis Caitriona Ryan, Baylor University Medical Center, Dallas, TX, United States; Murali Sundaram, AbbVie Inc, North Chicago, IL, United States; Min Yang, Analysis Group, Inc, Boston, MA, United States; Ravi Goyal, Analysis Group, Inc, Boston, MA, United States; Zhou Zhou, Analysis Group, Inc, Boston, MA, United States; James Signorovitch, Analysis Group, Inc, Boston, MA, United States Objective: A 90% reduction from baseline on the Psoriasis Area and Severity Index (PASI90) has been used to assess the effectiveness of biologic treatments in psoriasis. This study compared PASI90 response between patients with psoriasis who were treated with adalimumab and placebo, and identified predictors of PASI90 response among the adalimumab-treated patients. Methods: Patients with moderate to severe psoriasis who were randomized to adalimumab or placebo in 2 phase 3 clinical trials were included in the analyses (REVEAL, NCT00237887; CHAMPION, NCT00235820). The double-blind follow-up period in both studies was 16 weeks. The cumulative rate of achieving PASI90 response was compared between adalimumab and placebo arms using Kaplan-Meier analysis and a log-rank test. A subgroup analysis was conducted for patients achieving PASI50 at any time during the 16 week follow-up period. A baseline prediction model for achievement of PASI90 response at Week 16 was developed among patients receiving adalimumab in REVEAL and validated using independent data from CHAMPION. Results: In the pooled trial population (adalimumab n ¼ 921; placebo n ¼ 451), the mean age was 44 years and 67% were male. The cumulative rate of PASI90 response by Week 16 was 53.6% for adalimumab and 4.1% for placebo (P \.001). Among patients achieving PASI50, which occurred for 90.2% receiving adalimumab and 23.5% receiving placebo, the cumulative rate of PASI90 achievement by week 16 was 65.3% for adalimumab and 23.0% for placebo (P \ .001). In data from adalimumab-treated patients in REVEAL (n ¼ 787), significant predictors of PASI90 response included younger age (odds ratio per year [OR] 0.98), male gender (OR 1.49), and lower weight (#75 kg, OR 3.40; 75e100 kg, OR 2.66; reference [125 kg). The model provided moderate predictive value (C statistic 0.65) when validated among adalimumab-treated patients in CHAMPION (n ¼ 104). Conclusions: The majority of adalimumab-treated patients achieved PASI90 response by Week 16. Among those adalimumab-treated patients achieving PASI50, nearly two-thirds ultimately achieved a PASI90 response. In contrast, fewer
MAY 2016
3386 Predictors of response to tofacitinib or etanercept in a phase 3 randomized, noninferiority study in patients with moderate to severe chronic plaque psoriasis Jo Lambert, Ghent University Hospital, Ghent, Belgium; Robert Strohal, Federal Academic Teaching Hospital of Feldkirch, Feldkirch, Austria; Claudia de la Cruz, Clınica Dermacross, Santiago, Chile; Diamant Thac¸i, Comprehensive Center for Inflammation Medicine, University Medical School, Schleswig-Holstein Campus, L€ ubeck, Germany; Herve Bachelez, Sorbonne Paris Cite Universite Paris Diderot, APHP H^ opital Saint-Louis, Paris, France; Lars Iversen, Aarhus University Hospital, Aarhus C, Denmark; Scott Rottinghaus, Pfizer Inc, Groton, CT, United States; Anna Tallman, Pfizer Inc, New York, NY, United States; Huaming Tan, Pfizer Inc, Groton, CT, United States; Gabriel Berstein, Pfizer Inc, Cambridge, MA, United States Background: Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. In the phase 3 study, OPT Compare, tofacitinib 10 mg BID was noninferior to etanercept 50 mg BIW. Objective: To ascertain whether certain baseline characteristics can predict a differential response to tofacitinib 10 mg BID vs etanercept 50 mg BIW. Methods: In this posthoc analysis of data from OPT Compare (NCT01241591), efficacy at 12 weeks of tofacitinib (10 mg BID) vs etanercept (50 mg BIW) was evaluated overall and in subgroups according to the following baseline characteristics: age, gender, race, geographic region, PASI, PGA, affected BSA, weight, BMI, CRP, and treatment history. Descriptive statistics for differences (and 95% CIs) in the percentage of PASI75 responders between the tofacitinib and etanercept groups were compared. Results: Of the 1101 patients enrolled in this study who received study medication/placebo, 330 and 335 received tofacitinib 10 mg BID and etanercept 50 mg BIW, respectively. Baseline characteristics were similar between these two treatment groups: most patients were male (70e72%) and white (86e87%). Mean body weight was 83e85 kg, mean PASI score was 23 in both groups, mean affected BSA was 31e32%. In addition, 93e94% had received prior systemic agents, and 72% in both groups had received prior phototherapy. Overall, PASI75 and PASI90 responses at Week 12 were achieved by 63.6% and 36.1% of tofacitinib recipients and 58.8% and 32.2% of etanercept recipients, respectively. The percentage of PASI75 responders at Week 12 was similar between the tofacitinib and etanercept groups when analyzed by age, race, geographic region, baseline PASI, PGA, affected BSA, and treatment history. Subgroups with higher PASI75 response at Week 12 to tofacitinib vs etanercept were females (difference 16.6%, 95% CI 3.1%, 30.1%); patients with higher CRP ($0.3 mg/dL; difference 12.8%, 95% CI 1.6%, 24.0%); heavier patients (90 to \120 kg; difference 13.3%, 95% CI 0.45%, 26.2%); and patients with higher BMI (30 to \40 kg/m2; difference 19.5%, 95% CI 6.8%, 32.3%). No subgroup of patients responded better to etanercept than tofacitinib. Conclusion: Tofacitinib 10 mg BID was noninferior to etanercept 50 mg BIW and the difference in efficacy between the treatment groups was small for most subgroups of patients. Nevertheless, females, patients with higher baseline CRP, and heavier patients responded better to tofacitinib than to etanercept. This study was funded by Pfizer Inc. Medical writing, under guidance from the authors, was provided by Complete Medical Communications and funded by Pfizer Inc.
J AM ACAD DERMATOL
AB263
than a quarter of placebo-treated patients with a PASI50 response achieved a PASI90 response. Younger age, male gender, and lower weight were associated with a greater chance of achieving PASI90 with adalimumab. Design, study conduct, and financial support for the study were provided by AbbVie; AbbVie participated in the interpretation of data, review, and approval of the abstract; all authors contributed to the development of the publication.
Case report: A 45-year-old man hypertensive, diabetic and no drug allergies, with a history of severe, recalcitrant psoriasis for which he received biologic treatments (ustekinumab and etanercept) without control of the disease. He started adalimumab and within the second month, there was significant clinical improvement. However, 10 weeks after commencing treatment, he developed new cutaneous lesions consisting of erythematous papules, with central scaling, affecting the trunk, the buttocks, and extremities, sparing the face, palms, and soles. These were asymptomatic and did not coincide with intercurrent illness or other new pharmacologic therapy. Microscopic examination of a skin biopsy showed findings consistent with PLC. No clonal rearrangement of the TCR was detected. It was decided, on the assumption of a synergistic action, to start methotrexate (MTX) therapy (15 mg/week) and adalimumab was continued because of the severity of psoriasis. Complete remission was achieved in 6 weeks with residual pigmentation and bowel disease was controlled. This was discontinued but 15 days later PLC recurred and MTX was again introduced and led to new remission. Discussion: The pathogenesis of PLC is not well understood. However, CD4+ T helper cells are heavily implicated, and alterations in T-cell function and cytokine production, secondary to TNF inhibition, may be responsible for triggering the disease. The treatment of PLC relies on antibiotics and/or phototherapy. In case of failure, immunosuppressants are recommended. The course of PLC is variable, spontaneous regression is possible. MTX is effective for PLC, and represents an interesting therapeutic option because of the synergistic action of MTX and TNF-a inhibitors in psoriasis. Commercial support: None identified.
2571 Predicting PASI90 response among adalimumab-treated patients with moderate to severe psoriasis Caitriona Ryan, Baylor University Medical Center, Dallas, TX, United States; Murali Sundaram, AbbVie Inc, North Chicago, IL, United States; Min Yang, Analysis Group, Inc, Boston, MA, United States; Ravi Goyal, Analysis Group, Inc, Boston, MA, United States; Zhou Zhou, Analysis Group, Inc, Boston, MA, United States; James Signorovitch, Analysis Group, Inc, Boston, MA, United States Objective: A 90% reduction from baseline on the Psoriasis Area and Severity Index (PASI90) has been used to assess the effectiveness of biologic treatments in psoriasis. This study compared PASI90 response between patients with psoriasis who were treated with adalimumab and placebo, and identified predictors of PASI90 response among the adalimumab-treated patients. Methods: Patients with moderate to severe psoriasis who were randomized to adalimumab or placebo in 2 phase 3 clinical trials were included in the analyses (REVEAL, NCT00237887; CHAMPION, NCT00235820). The double-blind follow-up period in both studies was 16 weeks. The cumulative rate of achieving PASI90 response was compared between adalimumab and placebo arms using Kaplan-Meier analysis and a log-rank test. A subgroup analysis was conducted for patients achieving PASI50 at any time during the 16 week follow-up period. A baseline prediction model for achievement of PASI90 response at Week 16 was developed among patients receiving adalimumab in REVEAL and validated using independent data from CHAMPION. Results: In the pooled trial population (adalimumab n ¼ 921; placebo n ¼ 451), the mean age was 44 years and 67% were male. The cumulative rate of PASI90 response by Week 16 was 53.6% for adalimumab and 4.1% for placebo (P \.001). Among patients achieving PASI50, which occurred for 90.2% receiving adalimumab and 23.5% receiving placebo, the cumulative rate of PASI90 achievement by week 16 was 65.3% for adalimumab and 23.0% for placebo (P \ .001). In data from adalimumab-treated patients in REVEAL (n ¼ 787), significant predictors of PASI90 response included younger age (odds ratio per year [OR] 0.98), male gender (OR 1.49), and lower weight (#75 kg, OR 3.40; 75e100 kg, OR 2.66; reference [125 kg). The model provided moderate predictive value (C statistic 0.65) when validated among adalimumab-treated patients in CHAMPION (n ¼ 104). Conclusions: The majority of adalimumab-treated patients achieved PASI90 response by Week 16. Among those adalimumab-treated patients achieving PASI50, nearly two-thirds ultimately achieved a PASI90 response. In contrast, fewer
MAY 2016
3386 Predictors of response to tofacitinib or etanercept in a phase 3 randomized, noninferiority study in patients with moderate to severe chronic plaque psoriasis Jo Lambert, Ghent University Hospital, Ghent, Belgium; Robert Strohal, Federal Academic Teaching Hospital of Feldkirch, Feldkirch, Austria; Claudia de la Cruz, Clınica Dermacross, Santiago, Chile; Diamant Thac¸i, Comprehensive Center for Inflammation Medicine, University Medical School, Schleswig-Holstein Campus, L€ ubeck, Germany; Herve Bachelez, Sorbonne Paris Cite Universite Paris Diderot, APHP H^ opital Saint-Louis, Paris, France; Lars Iversen, Aarhus University Hospital, Aarhus C, Denmark; Scott Rottinghaus, Pfizer Inc, Groton, CT, United States; Anna Tallman, Pfizer Inc, New York, NY, United States; Huaming Tan, Pfizer Inc, Groton, CT, United States; Gabriel Berstein, Pfizer Inc, Cambridge, MA, United States Background: Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. In the phase 3 study, OPT Compare, tofacitinib 10 mg BID was noninferior to etanercept 50 mg BIW. Objective: To ascertain whether certain baseline characteristics can predict a differential response to tofacitinib 10 mg BID vs etanercept 50 mg BIW. Methods: In this posthoc analysis of data from OPT Compare (NCT01241591), efficacy at 12 weeks of tofacitinib (10 mg BID) vs etanercept (50 mg BIW) was evaluated overall and in subgroups according to the following baseline characteristics: age, gender, race, geographic region, PASI, PGA, affected BSA, weight, BMI, CRP, and treatment history. Descriptive statistics for differences (and 95% CIs) in the percentage of PASI75 responders between the tofacitinib and etanercept groups were compared. Results: Of the 1101 patients enrolled in this study who received study medication/placebo, 330 and 335 received tofacitinib 10 mg BID and etanercept 50 mg BIW, respectively. Baseline characteristics were similar between these two treatment groups: most patients were male (70e72%) and white (86e87%). Mean body weight was 83e85 kg, mean PASI score was 23 in both groups, mean affected BSA was 31e32%. In addition, 93e94% had received prior systemic agents, and 72% in both groups had received prior phototherapy. Overall, PASI75 and PASI90 responses at Week 12 were achieved by 63.6% and 36.1% of tofacitinib recipients and 58.8% and 32.2% of etanercept recipients, respectively. The percentage of PASI75 responders at Week 12 was similar between the tofacitinib and etanercept groups when analyzed by age, race, geographic region, baseline PASI, PGA, affected BSA, and treatment history. Subgroups with higher PASI75 response at Week 12 to tofacitinib vs etanercept were females (difference 16.6%, 95% CI 3.1%, 30.1%); patients with higher CRP ($0.3 mg/dL; difference 12.8%, 95% CI 1.6%, 24.0%); heavier patients (90 to \120 kg; difference 13.3%, 95% CI 0.45%, 26.2%); and patients with higher BMI (30 to \40 kg/m2; difference 19.5%, 95% CI 6.8%, 32.3%). No subgroup of patients responded better to etanercept than tofacitinib. Conclusion: Tofacitinib 10 mg BID was noninferior to etanercept 50 mg BIW and the difference in efficacy between the treatment groups was small for most subgroups of patients. Nevertheless, females, patients with higher baseline CRP, and heavier patients responded better to tofacitinib than to etanercept. This study was funded by Pfizer Inc. Medical writing, under guidance from the authors, was provided by Complete Medical Communications and funded by Pfizer Inc.
J AM ACAD DERMATOL
AB263