Paradoxical Psoriasis During IL-17 Blockage: Two Memorable Patients

47 year-old man who suffered for plaque psoriasis since 2013 was previously treated with topicals, UVB photherapy, acitretin, methotrexate and adalimumab (Imraldi®) with scarce response. Brodalumab (IL-17 receptor chain A blocking antibody) at 210 mg sc day 0, week-1, week-2 and every 2 weeks was initiated (baseline PASI of 16) with fast improvement of psoriasis (PASI-90 at week 4) and new onset of erythema, pustules and pain in the palmoplantar area after each subcutaneous Brodalumab administration and progressive improvement after 5-8 days.

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ENCORE 601: A phase II study of entinostat (ENT) in combination with pembrolizumab (PEMBRO) in patients with melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9529 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9529-9529 ◽

Cited By ~ 13

Author(s):

Melissa Lynne Johnson ◽

Rene Gonzalez ◽

Mateusz Opyrchal ◽

Dmitry Gabrilovich ◽

Peter Ordentlich ◽

...

Keyword(s):

Checkpoint Inhibitors ◽

Objective Response ◽

Braf Inhibitor ◽

Suppressor Cells ◽

Gene Signature ◽

Phase 2 ◽

Blocking Antibody ◽

Best Response ◽

Investigation Methods ◽

Previously Treated

9529 Background: Entinostat is an oral, class I selective histone deacetylase inhibitor shown preclinically to enhance immune checkpoint inhibitor activity by regulation of immune suppressor cells in the tumor microenvironment. ENCORE 601 is designed to evaluate safety and efficacy of ENT in combination with PEMBRO. Phase 1b identified ENT 5 mg PO weekly and PEMBRO 200 mg IV every 3 weeks as the recommended Phase 2 dose for further investigation. Methods: Phase 2 of ENCORE 601 employs a Simon 2-stage design to assess activity across 3 cohorts: 1) NSCLC not previously treated with a PD-1/L1 blocking antibody, 2&3) NSCLC & melanoma previously progressing on or after a PD-1/L1 blocking antibody. Patients were enrolled irrespective of PD-L1 expression levels. The primary endpoint is ORR as assessed by irRECIST. Results of the first stage of Cohort 3 are reported. Criteria for advancing to Stage 2 are ≥2 responses out of 13 evaluable patients. Results: Stage 1 enrollment has been completed (n = 13). All patients received a prior PD-1 inhibitor; in addition, 7 patients received prior ipilimumab and 2 patients received a prior BRAF inhibitor. 9 patients are still on treatment; 4 patients have discontinued due to progression. To date, 1 confirmed and 1 unconfirmed objective response have been observed. The confirmed response (PR) was in a patient who was previously treated with ipilimumab/nivolumab for 6 months (best response of SD with subsequent progression on therapy). Treatment-related AEs occurred in 5 patients (most common being nausea and fatigue occurring in 2 patients); one patient experienced Gr3/4 events (fatigue and rash). Blood samples and pre-treatment biopsies were obtained in all patients along with paired post-treatment biopsies in 8 patients. Evaluation of PD-L1 expression, gene expression, myeloid and lymphoid compartments in blood and tumor samples is in progress. Of note, the patient with a confirmed PR converted from a PD-L1 negative, non-inflamed gene signature to PD-L1 positive, inflamed after 2 weeks of treatment. Conclusions: ENT combined with PEMBRO demonstrates acceptable safety and encouraging preliminary activity in melanoma patients refractory to checkpoint inhibitors. Clinical trial information: NCT02437136.

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Severe de novo Ulcerative Colitis following Ixekizumab Therapy

Case Reports in Gastroenterology ◽

10.1159/000493922 ◽

2018 ◽

Vol 12 (3) ◽

pp. 617-621 ◽

Cited By ~ 9

Author(s):

Jobin Philipose ◽

Moiz Ahmed ◽

Pretty S. Idiculla ◽

Stephen M. Mulrooney ◽

Vivek V. Gumaste

Keyword(s):

Ulcerative Colitis ◽

Plaque Psoriasis ◽

Randomized Trials ◽

De Novo ◽

Young Male ◽

Chronic Plaque Psoriasis ◽

Unique Case ◽

Interleukin 17A ◽

Inflammatory Bowel ◽

New Onset

Ixekizumab is a selective monoclonal antibody targeting interleukin-17A, approved for the treatment of chronic plaque psoriasis. It has rarely been associated with inflammatory bowel disease (IBD) in randomized trials only. We report a unique case of severe new-onset ulcerative colitis in a young male complicated by cytomegalovirus infection who was on ixekizumab therapy for plaque psoriasis. We recommend that clinicians should exercise caution before prescribing ixekizumab as it seems to induce and exacerbate IBD.

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Efficacy and safety of infliximab therapy in plaque psoriasis patients previously treated with etanercept: Analysis of PSUNRISE

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2009.11.511 ◽

2010 ◽

Vol 62 (3) ◽

pp. AB133 ◽

Cited By ~ 1

Keyword(s):

Plaque Psoriasis ◽

Infliximab Therapy ◽

Efficacy And Safety ◽

Previously Treated

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New-Onset Vitiligo Following Etanercept for Ankylosing Spondylitis

SKIN The Journal of Cutaneous Medicine ◽

10.25251/skin.3.5.7 ◽

2019 ◽

Vol 3 (5) ◽

pp. 338-340

Author(s):

Carly Dunn ◽

Stacy L. McMurray ◽

Allison Jones ◽

Debendra Pattanaik

Keyword(s):

Ankylosing Spondylitis ◽

Skin Diseases ◽

Joint Disease ◽

Necrosis Factor Alpha ◽

Inflammatory Conditions ◽

Immune Mediated ◽

Previously Treated ◽

Factor Alpha ◽

Necrosis Factor ◽

New Onset

Tumor Necrosis Factor-alpha (TNF-a) inhibitors, are used widely to treat a variety of chronic inflammatory conditions such as ankylosing spondylitis, Crohn’s disease, rheumatoid arthritis, and psoriasis. Recently, there has been an increase in the number of reports of immune-mediated skin diseases, such as lichen planus, psoriasis, granuloma annulare, following the initiation of TNF-a inhibitors. We present a patient with ankylosing spondylitis previously treated with adalimumab who developed vitiligo shortly after switching to etanercept to achieve better control of his joint disease.

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Ixekizumab—An Effective and Safe Treatment for Moderate-to-Severe Plaque Psoriasis in Patients Previously Treated With Other IL-17 Inhibitors: Results From IXORA-P

Journal of Psoriasis and Psoriatic Arthritis ◽

10.1177/2475530319867095 ◽

2019 ◽

Vol 4 (4) ◽

pp. 180-185 ◽

Cited By ~ 1

Author(s):

Kim Papp ◽

Andrew Blauvelt ◽

John Sullivan ◽

Yayoi Tada ◽

Paula Polzer ◽

...

Keyword(s):

Plaque Psoriasis ◽

Therapeutic Option ◽

Previous Treatment ◽

Severity Index ◽

Interleukin 17 ◽

Severe Plaque Psoriasis ◽

Previously Treated ◽

Double Blinded ◽

The Impact ◽

Blinded Trial

Background: The impact of treatment with interleukin 17 (IL-17) inhibitors on the efficacy of subsequent IL-17 inhibitor therapy is unknown. Objective: To evaluate the impact of previous treatment with IL-17 inhibitors on the 52-week efficacy of ixekizumab in patients with moderate-to-severe psoriasis. Methods: In a phase 3, randomized, double-blinded trial (IXORA-P; NCT02513550), patients with moderate-to-severe plaque psoriasis were randomized (2:1:1) to ixekizumab 80 mg every 2 weeks (IXE Q2W, n = 611), every 4 weeks (IXE Q4W, n = 310), or IXE Q4W/IXE Q2W dose adjustment (per predefined criteria; n = 306). Psoriasis Area and Severity Index 75%, 90%, and 100% response rates (PASI 75, PASI 90, and PASI 100) were assessed. Results: Overall, 288 (23.5%) of 1227 patients were IL-17 inhibitor experienced (brodalumab, 22.6%; secukinumab, 1.1%). The PASI 75, 90, and 100 at week 52 were similar between IL-17 inhibitor-naive and IL-17 inhibitor-experienced patients. The PASI 75 at week 52 for IL-17 inhibitor-naive and -experienced patients was 85% and 89% (IXE Q2W), 79% and 81% (IXE Q4W), and 83% and 85% (IXE Q4W/IXE Q2W), respectively. The PASI 90 at week 52 for IL-17 inhibitor-naive and -experienced patients was 79% and 82% (IXE Q2W), 65% and 67% (IXE Q4W), and 73% and 75% (IXE Q4W/IXE Q2W), respectively. The PASI 100 at week 52 for IL-17 inhibitor-naive and -experienced patients was 60% and 59% (IXE Q2W), 44% and 42% (IXE Q4W), and 49% and 52% (IXE Q4W/IXE Q2W), respectively. Safety findings were generally similar between IL-17 inhibitor-naive and -experienced patients. Conclusion: Ixekizumab was demonstrated to be an effective and safe therapeutic option for patients previously treated with other IL-17 inhibitors.

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Real-life Effectiveness and Safety of Risankizumab in Moderate-to-severe Plaque Psoriasis: A 40-week Multicentric Retrospective Study

Acta Dermato Venereologica ◽

10.2340/actadv.v101.283 ◽

2021 ◽

Author(s):

Riccardo G. Borroni ◽

Piergiorgio Malagoli ◽

Luigi Gargiulo ◽

Mario Valenti ◽

Giulia Pavia ◽

...

Keyword(s):

Retrospective Study ◽

Plaque Psoriasis ◽

Real Life ◽

Severity Index ◽

First Line ◽

Life Effectiveness ◽

Real Life Setting ◽

Humanized Monoclonal Antibody ◽

Previously Treated ◽

Interleukin 23

Risankizumab is a humanized monoclonal antibody that binds the p19 subunit of interleukin-23. It is approved for treatment of moderate-severe chronic plaque psoriasis. This retrospective study included 66 consecutive adults with moderate-to-severe psoriasis vulgaris treated with risankizumab in monotherapy up to week 40 in a “real-life” setting. At week 40, 98.7%, 85.7% and 62.3% of patients achieved a Psoriasis Area and Severity Index (PASI) reduction ≥ 75% (PASI 75), PASI 90 and PASI 100, respectively. Patients who had not responded to 2 or more previous biologic treatments were significantly less likely to achieve PASI 75/90 at week 16 and PASI 90/100 at week 40 compared with those who had been previously treated with only 1 biologic, and compared with those treated with risankizumab as a first-line biologic. Increasing body mass index decreased the chances of reaching PASI 90 at week 40. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment. These data suggest that the efficacy of risankizumab for plaque psoriasis in “real-life” clinical practice could differ from pivotal clinical trials data.

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Severe drug-associated colitis with Crohn’s features in setting of ixekizumab therapy for chronic plaque psoriasis

BMC Gastroenterology ◽

10.1186/s12876-021-01936-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xin Mu ◽

John Fardy ◽

Stephanie Reid ◽

Julia Trahey

Keyword(s):

Inflammatory Bowel Disease ◽

Plaque Psoriasis ◽

Interleukin 17 ◽

Chronic Plaque Psoriasis ◽

Case Presentation ◽

Inflammatory Bowel ◽

Potential Risks ◽

Inflammatory Changes ◽

Disease Free ◽

New Onset

Abstract Background Ixekizumab is monoclonal antibody targeted against interleukin-17 (IL-17) and has been approved for use in chronic plaque psoriasis. Despite its efficacy in treating psoriasis, concerns have been raised regarding Ixekizumab’s potential to induce and exacerbate inflammatory bowel disease (IBD). Case presentation Here we report the new onset of severe drug-associated colitis with surgical complications in a 45-year-old male patient who was receiving Ixekizumab therapy for chronic plaque psoriasis. Review of the patient’s colonic pathology demonstrated acute inflammatory changes with features of Crohn’s disease. The patient remained disease-free 9-months following his hospitalization and cessation of Ixekizumab. Conclusions This case raises suspicion for an association between Ixekizumab and IBD and calls on clinicians to have heightened awareness of potential risks before prescribing anti-IL-17 agents.

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