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Figure 1.
Distribution of patients using biological agents prior to adalimumab therapy.

Distribution of patients using biological agents prior to adalimumab therapy.

Figure 2.
Results of adalimumab treatment for psoriasis in the 49 study patients.

Results of adalimumab treatment for psoriasis in the 49 study patients.

Table. 
Incidence of Adverse Events in 49 Patients Taking Adalimumaba
Incidence of Adverse Events in 49 Patients Taking Adalimumaba
1.
Graves  JENunley  KHeffernan  MP Off-label uses of biologics in dermatology: rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept (part 2 of 2). J Am Acad Dermatol 2007;56 (1) e55- e79
PubMedArticle
2.
Boehncke  WHPrinz  JGottlieb  AB Biologic therapies for psoriasis: a systematic review. J Rheumatol 2006;33 (7) 1447- 1451
PubMed
3.
Baert  FNoman  MVermeire  S  et al.  Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003;348 (7) 601- 608
PubMedArticle
4.
 HUMIRA (adalimumab) [package insert].  North Chicago, IL Abbott Laboratories2004;
5.
Gordon  KBLangley  RGLeonardi  C  et al.  Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol 2006;55 (4) 598- 606
PubMedArticle
Research Letter
June 01, 2008

Sustained Efficacy and Safety of Adalimumab in Psoriasis Treatment: A Retrospective Study of 49 Patients With and Without a History of TNF-α Antagonist Treatment

Arch Dermatol. 2008;144(6):804-806. doi:10.1001/archderm.144.6.804

Of the 3 available tumor necrosis factor α (TNF-α) antagonists, infliximab and etanercept are approved for treatment of moderate to severe, chronic, plaque-type psoriasis.1,2 Although no standardized comparison trial exists, infliximab appears to be the most rapidly effective, but this initial efficacy is often eventually lost with the development of human antichimeric antibodies in 15% to 69% of patients.13

Adalimumab, the third TNF-α antagonist, is currently in phase III trials for psoriasis treatment. As a fully human IgG1 monoclonal antibody, it is expected to have less immunogenicity and secondary antibody-mediated loss of efficacy.1,2 Despite clinical reports of antiadalimumab antibodies, impact on long-term clinical response is unclear.4

One recent study demonstrated adalimumab to be efficacious for psoriasis treatment of patients with no previous exposure to TNF antagonists.5 Since it is uncertain whether long-term response to adalimumab (≥12 months) can be sustained in patients for whom other anti-TNF therapy has failed to treat moderate to severe plaque psoriasis, we address this question retrospectively in 49 patients with and without prior use of TNF-α blockade.

Methods

This retrospective medical chart review includes 49 patients seen at the Baylor College of Medicine dermatology clinic. All patients had moderate to severe psoriasis based on the physician's global assessment (PGA) and had started treatment with adalimumab injections at least 12 months previously. All were screened for tuberculosis. Patients who had undergone prior therapy with biological agents were switched to adalimumab therapy only after they had experienced lack or loss of efficacy with their prior treatment. Patients switched from infliximab therapy had a washout period of at least 2 months, and those switched from etanercept or efalizumab had a washout period of at least 2 weeks.

Patients started treatment with adalimumab, 40 mg weekly, for 12 weeks. All were reassessed at 3 months. Patients whose disease was determined to be “clear” or “almost clear” by PGA had their doses decreased to once every 2 weeks, while the remainder continued weekly dosing for another 3 months. Patients were then reassessed at 3- to 6-month intervals, during which the dermatologist decreased the dosing frequency to once every 2 weeks or continued the weekly schedule, depending on individual response.

The clinical end point was defined as worsening PGA despite continuous adalimumab treatment or the occurrence of adverse events necessitating discontinuation of adalimumab treatment. Treatment failure was differentiated into primary lack of efficacy (no clinical response seen), secondary loss of efficacy (PGA degrades to lower than clear or almost clear after an initial response), and limited efficacy (clinical response seen, but patient never achieves clear or almost clear status).

Results

Thirty-nine patients had prior exposure to biological agents (80%). Thirty-seven had prior anti–TNF-α therapy (76%) (Figure 1). No complications were observed during transitions from prior biological agents.

Forty-three patients achieved clear to almost clear status at 3 months (88%), 3 at 6 months, and 1 at 9 months, while 2 continued to received weekly dosing because they did not achieve clear to almost clear status. Two patients, whose dose had been decreased to 1 every 2 weeks at 3 months, resumed weekly dosing at 9 months. Sustained efficacy at 12 months was observed in 38 patients (78%). Of the 39 previously treated with biological agents, 31 experienced sustained efficacy with adalimumab (79%). Of the 37 who had been treated with TNF-α antagonists, 29 had a sustained response (78%). Figure 2 summarizes reasons for discontinuation of adalimumab treatment in 9 patients prior to 12 months.

Comment
Efficacy

In a multicenter study of adalimumab in patients with psoriasis who had never been exposed to TNF-α antagonists, PGA measurements in the weekly treatment group showed a decline in the number of patients with clear or almost clear status from 76% at week 12 to 52% at week 60.5 The PGA of clear or almost clear was comparable at 12 (49%) and 60 (44%) weeks in the group receiving 1 dose every 2 weeks. Fourteen patients (11%) withdrew from the study between weeks 24 and 60 secondary to lack of efficacy.5 Our patients' dosing regimen was based on this study's dosage arms.

Our study contributes further evidence that most patients with moderate to severe psoriasis who initially respond to adalimumab continue to experience efficacy at 1 year (88%). In addition, our study demonstrates that psoriasis in most patients previously treated with other TNF-α antagonists will respond to adalimumab. Approximately 78% of adalimumab patients treated with etanercept, infliximab, or both continued to have almost clear to clear PGA status at 12 months.

Safety

In the multicenter trial conducted by Gordon et al,5 9% of patients discontinued therapy owing to an adverse event (AE). The numbers of patients in the placebo and treatment groups who experienced any AE during the first 12 weeks were comparable, but no serious AEs occurred in the placebo group. The investigators questioned whether the reported AEs were directly attributable to treatment.5

The incidence of AEs in our study was 14%. Five patients developed serious AEs (2 cellulitis and 1 each unexplained fevers, back pain, and pyelonephritis) that resulted in treatment termination (10%) (Table). One patient developed a serious AE (squamous cell carcinoma) but opted to continue treatment.

Conclusion

Results from this study support the idea that patients with psoriasis who have received prior TNF-α antagonists can expect sustained clinical response to adalimumab. Although our study is limited by retrospective design and small sample size, it adds to the collective understanding of the therapeutic role of adalimumab in the treatment of psoriasis.

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Article Information

Correspondence: Dr Hsu, Department of DermatologyBaylor College of Medicine, 6620 Main St, Ste 1425, Houston, TX 77030 (shsu@bcm.edu).

Author Contributions: Dr Hsu 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 disign: Van and Hsu. Acquisition of data:Van and Modi. Analysis and interpretation of data: Ban, Modi, Yang, and Hsu. Drafting of the manuscript: Van, Modi, and Yang. Critical revision of the manuscript for important intellectual content: Van, Modi, Yang, and Hsu. Statistical analysis:Van. Study supervision: Yang and Hsu.

Financial Disclosure: Dr Hsu has served on advisory boards for Abbott, Amgen, Biogen Idec, Centocor, Genentech, and Medicis. She has also been an investigator for Centocor and Genentech.

Additional Information: This article was accepted for publication prior to January 18, 2008, the date the US Food and Drug Administration approved the use of adalimumab for the treatment of moderate to severe chronic plague-type psoriasis in adults.

References
1.
Graves  JENunley  KHeffernan  MP Off-label uses of biologics in dermatology: rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept (part 2 of 2). J Am Acad Dermatol 2007;56 (1) e55- e79
PubMedArticle
2.
Boehncke  WHPrinz  JGottlieb  AB Biologic therapies for psoriasis: a systematic review. J Rheumatol 2006;33 (7) 1447- 1451
PubMed
3.
Baert  FNoman  MVermeire  S  et al.  Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003;348 (7) 601- 608
PubMedArticle
4.
 HUMIRA (adalimumab) [package insert].  North Chicago, IL Abbott Laboratories2004;
5.
Gordon  KBLangley  RGLeonardi  C  et al.  Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol 2006;55 (4) 598- 606
PubMedArticle
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