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Figure 1.
Psoriasis Area and Severity Index Scores
Psoriasis Area and Severity Index Scores

Percentage of patients whose Psoriasis Area and Severity Index scores had improved to 25, 50, or 75 on day 56.

Figure 2.
Resolution of Psoriatic Plaques on a Patient’s Knees
Resolution of Psoriatic Plaques on a Patient’s Knees

This patient’s Psoriasis Area and Severity Index Score improved to 75. A, Day zero (before treatment). B, Day 42 (before the third dose).

1.
Mee  JB, Cork  MJ, di Giovine  FS, Duff  GW, Groves  RW.  Interleukin-1: a key inflammatory mediator in psoriasis? Cytokine. 2006;33(2):72-78.
PubMedArticle
2.
Garrone  P, Djossou  O, Fossiez  F,  et al.  Generation and characterization of a human monoclonal autoantibody that acts as a high affinity interleukin-1 α specific inhibitor. Mol Immunol. 1996;33(7-8):649-658.
PubMedArticle
3.
Bito  T, Nishikawa  R, Hatakeyama  M,  et al.  Influence of neutralizing antibodies to adalimumab and infliximab on the treatment of psoriasis. Br J Dermatol. 2014;170(4):922-929.
PubMedArticle
4.
Committee for Medicinal Products for Human Use. Guideline on Clinical Investigation of Medicinal Products Indicated for the Treatment of Psoriasis: CHMP/EWP/2454/02 Corr. London, England: European Medicines Agency; 2004
5.
Hong  DS, Hui  D, Bruera  E,  et al.  MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol. 2014;15(6):656-666.
PubMedArticle
Research Letter
May 2015

Open-Label Trial of MABp1, a True Human Monoclonal Antibody Targeting Interleukin 1α, for the Treatment of Psoriasis

Author Affiliations
  • 1Westlake Dermatology and Cosmetic Surgery, Austin, Texas
  • 2Department of Dermatology, University of Michigan, Ann Arbor
  • 3XBiotech USA, Austin, Texas
JAMA Dermatol. 2015;151(5):555-556. doi:10.1001/jamadermatol.2014.5391

MABp1is a true human monoclonal antibody specific for interleukin 1α (IL-1α), a key proinflammatory cytokine involved in sterile inflammation that is abundantly present in psoriatic skin lesions.1 MABp1 differs from previous generations of therapeutic antibodies in that it was cloned from an Epstein-Barr virus–immortalized human B cell that was isolated from an individual with endogenous anti–IL-1α antibodies, and it has not undergone any in vitro affinity maturation.2 Thus, there is potential for decreased antidrug antibody formation, which should lead to a profile of fewer adverse effects and less loss of effectiveness over time.3

Methods

Institutional review board approval was obtained before study initiation (clinicaltrials.gov Identifier: NCT01384630). Patients gave written consent before enrollment. Patients with a minimum Psoriasis Area and Severity Index (PASI) score of 12 and an affected body surface area of 5% were eligible to be enrolled in this open label, single-arm trial. Eight patients with a mean (SD) baseline PASI score of 13.8 (1.3) were enrolled; 5 patients had moderate to severe disease and 3 had moderate disease, as determined by a 7-point Physician Global Assessment.4 All patients were required to have discontinued prior systemic or phototherapies for 4 weeks (or 5 half-lives, which ever was longer) and topical therapies 2 weeks before initiation of treatment. Patients received 200 mg of MABp1 as a monotherapy, via subcutaneous administration, every 3 weeks and were followed up to day 56 to assess clinical efficacy through PASI scores and to day 70 to assess terminal pharmacokinetics. This trial was conducted from February 2012 until December 2012.

Results

Plasma MABp1 concentration was determined using a proprietary enzyme-linked immunosorbent assay and human anti-MABp1 humoral responses were assessed with a qualitative sandwich enzyme-linked immunosorbent assay. The half-life of the antibody was 8 days, and no antidrug antibodies were detected. There were few adverse events reported, and all were grade 1 (mild). Of these, only a single adverse event was likely to be directly related to therapy, a grade 1 injection-site reaction. Complete blood cell counts and serum chemistry analyses were assessed at every visit, and no clinically significant abnormalities were identified.

By day 56, 5 of 8 patients (63%) had an improved PASI score of 25, 3 of 8 (38%) had a PASI score of 50, and 1 of 8 (13%) had a PASI score of 75 (Figure 1). The mean (SD) PASI score decreased from 12.4 (2.9) at day zero to 8.1 (3.4) on day 56 (P = .02). Of the individual PASI components, erythema was affected most during this study, with a mean (SD) reduction of 36% (14%) noted on day 56 (P = .03). Figure 2 shows a clinical response from a patient who achieved a PASI score of 75.

Discussion

Although this study is limited by its small size and lack of a control group, the clinical responses and high tolerability that were observed are encouraging. With a half-life of 8 days and a dosage schedule of every 3 weeks, a steady-state concentration was not achieved. As with currently approved biological agents used to treat psoriasis, which are given in intervals of about 1 half-life for each drug, we anticipate that an increased dosage frequency may result in higher PASI responses.

No anti-MABp1 antibodies were detected during the study period. This is consistent with observations that used MABp1 in a larger study of patients with cancer.5 Although a larger dermatology cohort will be required to confirm this finding, the lack of antidrug antibodies in this population may lead to improved long-term results and fewer adverse effects.

Although this study has certain limitations, treatment with MABp1 showed a promising therapeutic response in patients with psoriasis. We anticipate that the clinical responses observed in this trial can be further improved with increased dosage frequency and/or a higher dose. The results presented here indicate that targeting IL-1α has a strong potential therapeutic value in treating psoriasis and may provide a novel future treatment of this often devastating disease.

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Article Information

Accepted for Publication: December 7, 2014.

Corresponding Author: Kyle M. Coleman, MD, Westlake Dermatology and Cosmetic Surgery, 8825 Bee Cave Rd, Austin, TX 78746.

Published Online: February 25, 2015. doi:10.1001/jamadermatol.2014.5391.

Author Contributions: Dr Stecher had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Coleman, Gudjonsson.

Acquisition, analysis, or interpretation of data: All Authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: Coleman, Gudjonsson.

Administrative, technical, or material support: Coleman.

Study supervision: All authors.

Conflict of Interest Disclosures: Dr Stecher reports being employed by and having stock options from XBiotech USA. Dr Gudjonsson reports being a consultant for XBiotech USA. No other disclosures were reported.

Funding/Support: This study was supported in part by Xbiotech USA.

Role of the Funder/Sponsor: XBiotech USA had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Trial Registration: clinicaltrials.gov Identifier: NCT01384630

References
1.
Mee  JB, Cork  MJ, di Giovine  FS, Duff  GW, Groves  RW.  Interleukin-1: a key inflammatory mediator in psoriasis? Cytokine. 2006;33(2):72-78.
PubMedArticle
2.
Garrone  P, Djossou  O, Fossiez  F,  et al.  Generation and characterization of a human monoclonal autoantibody that acts as a high affinity interleukin-1 α specific inhibitor. Mol Immunol. 1996;33(7-8):649-658.
PubMedArticle
3.
Bito  T, Nishikawa  R, Hatakeyama  M,  et al.  Influence of neutralizing antibodies to adalimumab and infliximab on the treatment of psoriasis. Br J Dermatol. 2014;170(4):922-929.
PubMedArticle
4.
Committee for Medicinal Products for Human Use. Guideline on Clinical Investigation of Medicinal Products Indicated for the Treatment of Psoriasis: CHMP/EWP/2454/02 Corr. London, England: European Medicines Agency; 2004
5.
Hong  DS, Hui  D, Bruera  E,  et al.  MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol. 2014;15(6):656-666.
PubMedArticle
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