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Therapy-resistant psoriasis treated with alefacept and subsequent narrow band ultraviolet B phototherapy with total clearing of psoriasis

  • Author(s): Scheinfeld, Noah
  • et al.
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Therapy-resistant psoriasis treated with alefacept and subsequent narrow band ultraviolet B phototherapy with total clearing of psoriasis.
Noah Scheinfeld MD JD
Dermatology Online Journal 11 (2): 7

St Lukes Roosevelt Hospital Center, New York NY. Scheinfeld@earthlink.net

Abstract

Combinations of therapeutic modalities have been utilized to meet the challenge of difficult to treat psoriasis. We report two cases of psoriasis, resistant to methotrexate and monotherapy with UVB, treated effectively with alefacept and concomitant narrow band UVB resulting in total disease clear.



Clinical synopses


Patient 1

The first patient developed psoriasis in 1990 in her early forties, with plaques appearing on her elbows, arms, and sacrum. Sun bathing and topical corticosteroid cream helped improve her appearance mildly. The patient received broad-band UVB over a period of about 10 months, which led to substantial clearing. Thereafter, the patient had outbreaks moderately controlled with topical corticosteroids.

At the end of 2000, the patient was hospitalized with pneumonia and received intravenous antibiotics. She experienced great stress due to the death of her husband. Thereafter, the patient experienced an outbreak of widespread disease on her arms, legs, torso, and scalp. She was treated with corticosteroids, calcipotriol, salicylic acid (all removed before phototherapy), and narrowband UVB 3 times a week for over a year with some thinning of lesions but no clearance. Phototherapy was discontinued. Topical treatment was continued in combination with methotrexate given for 7 months titered up from 7.5 mg by 2.5 mg each week to a dose of 30 mg a week (taking about 6 weeks). At 30 mg of methotrexate taken weekly, the patient experienced moderate clearing of her arms but no change in the plaques on her legs and torso.

In early 2003, the patient's methotrexate was discontinued; after 6 weeks she was treated with alefacept 15 mg intramuscularly for 12 weeks. After 4 weeks, the patient had experienced no change in her disease. At this point the patient was restarted on narrow band UVB. After about 10 weeks of 3 times a week treatments nbUVB phototherapy and no topical therapy, the patient's psoriasis cleared completely. The patient's nbUVB was continued for 12 more weeks give 3 times a week and then discontinued. The patient was then disease free for 36 weeks.


Patient 2

The second patient began to suffer from psoriasis in his early thirties; it eventually involved his entire body. In the early 1980s, he used topical corticosteroids and coal tar without improvement. The patient also used oral methotrexate, broad band UVB, and etretinate individually for extended periods without improvement. In the 1990s, the patient began to use psoralen and UVA for a long period; this mostly cleared his disease but it was very difficult for him to continue.

In the late 1990s, the patient received entanercept (50 mg BIW) without improvement. The patient then used cyclosporine for months to which he responded with great but not total improvement, but which he did not want to continue. The patient's psoriasis returned and affected most of his body after the cyclosporine was discontinued.

As a replacement for cyclosporine, the patient then received alefacept 15 mg IM for 12 weeks. Clearing did not occur during treatment with alefacept. Several weeks after treatment with alefacept was halted, the patient received phototherapy with narrowband UVB 3 times a week (nbUVB) with total clearance of this disease over 2-3 months. After 6-8 months, while still on nbUVB treatment, the patient's psoriasis returned to a more limited extent. The patient was then treated with alefacept 15 mg for 12 weeks and then narrowband UVB three times a week again and experienced clearing of his psoriasis over 2-3 months. After 8 months, while still on UVB 3 times a week, the patient's body was still clear of psoriasis but his scalp had become very pruritic and scaly despite topical therapy with corticosteroid foams and other agents. This scalp pruritus was helped somewhat by cortisone injections in his scalp but soon after the patient began to experience body pruritus. To abate the scalp rash and body pruritus, upon request of the patient, another course of alefacept was started with concomitant nbUVB, which after two injections has not changed the appearance or pruritus of the scalp.


Discussion

Effective treatment of therapy-resistant psoriasis continues to challenge patients and dermatologists. Combinations of therapeutic modalities have been utilized to meet this challenge. Methotrexate, cyclosporine, acetretin, and phototherapy, the four most effective modalities of the 1990s, do not help all psoriatics. Beginning in 2003, biologics joined the armamentarium of psoriatic treatments. Biologics are not a panacea and are not universally and or consistently effective.

Combinations of methotrexate, cyclosporine, acetretin and phototherapy have been found more effective than these agents used individually [1]. It would seem reasonable that combinations of biologic therapies with these agents or other biologics would also result in greater clinical improvement of patients than biologic monotherapy [2]. Tumor necrosis factor alpha blockers have been combined with methotrexate for rheumatoid arthritis to good effect [3]. The combination of biologics with nbUVB seems particularly useful because of the mild side effect profile associated with each.

Alefacept, an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human, has been approved for monotherapy of psoriasis [4]. Alefecept is capable of inducing remissions of psoriasis that last months [4]. Some patients do not experience significant clinical improvement even 1 or 2 months after a 12-week course of alefacept.

The solution to this slow or seeming nonresponse to alefacept for a patient with psoriasis could be subsequent phototherapy. The two patients reported herein demonstrate that even if phototherapy was previously been unsuccessful, if given subsequent to alefacept, complete clearing of psoriasis may be achieved. This is the case even when alefacept does not yet appear to have induced an improvement in disease 1 or 2 months after alefacept administration has been halted.

Clinical trials have found that the combination of alefacept with phototherapy is safe and more effective than alefacept alone [5, 6]. The types and frequencies of mild and serious adverse events are similar when alefacept is administered alone or in combination with phototherapy [7]. UVB and alefacept used in combination seemed to show greater improvement than alefacept combined with other therapies [8]. It has been recognized that alefacept may work after its administration has been discontinued. Thus it is possible that the improvement experienced by our patients was the result of the alefacept alone. Several factors suggest that alefacept and nbUVB were synergistic: (1) the first patient even 2 months after treatment with alefacept did not experience a change in disease, but after 12 weeks of phototherapy achieved total clearance, which had eluded her with previous phototherapy; (2) the second patient achieved total clearance with alefacept, a response that had eluded him with previous therapies of all sorts; and (3) the second patient, even while on nbUVB, experienced disease rebound that was abated only with 12 weeks of concomitant alefacept adminstration and nbUVB phototherapy (this persisted for 8 months) (5) most notably, when the second patient's psoriasis returned it started on his scalp, an area that did not benefit from phototherapy; and (6) one patient has PASI 100 improvement, an end point that is uncommon for monotherapy with alefacept. It would seem that the combination of alefacept and nbUVB was helpful to these patients and in particular that only the combination of the treatments was so ameliorative.

Although monotherapy with alefacept or nbUVB may be a very effective treatment for psoriasis, treatment must always be tailored to the individual patient and individual immune system. Interestingly, for patients in whom UVB, PUVA and retinoids were ineffective and for whom methotrexate and cyclosporine were inappropriate, alefacept could have a role in effective treatment [9]. It is interesting to speculate that treatment with alefacept in some way changes the population of T-cells so that they are more susceptible to the anti-T-cell effects of nbUVB. It is also possible that nbUVB and alefacept share have common and diverse or merely diverse immunomodulatory and immunosuppressive mechanisms.

Sound clinical studies provided a basis for the treatment of the two patients reported above. In a study of combination therapy with alefacept and narrow UVB light, 30 patients were randomized to either alefacept alone, alefacept plus 6 weeks of narrowband UVB, or alefacept plus 12 weeks of narrowband UVB [10, 11]. All of the patients receiving alefacept plus either course of UVB achieved PASI 75 (75 % or greater PASI improvement). It is interesting to note that 80 percent of subjects receiving alefacept alone achieved PASI 75.

Concomitant nbUVB and alefacept have been studied in clinical trials. The addition of nbUVB to alefacept treatment resulted in a faster reduction in PASI than alefacept monotherapy [12]. With the combination of nbUVB and alefacept, 38 percent of patients already achieved a 50 percent reduction in PASI after 2 weeks of treatment; 57 percent of patients achieved a ≥75 percent reduction in PASI after 4 weeks of treatment. In this study, all of the patients treated with alefacept and nbUVB achieved a reduction from baseline PASI of ≥75 percent, and approximately 76 percent achieved a PGA of clear or almost clear. For patients who achieved a ≥75 percent PASI reduction 2 weeks after the last dose, all of the patients on alefacept monotherapy and approximately 80 percent of patients on the combination treatment arms maintained their response through the 12-week period (likely because patient who would not respond to UVB initially were more difficult to treat.

There are drawbacks to using alefacept and phototherapy in combination. The cost and inconvenience as compared with monotherapy of each agent alone are greater. This combination, although apparently safe, could have unforeseen side effects. Moreover, it is uncertain if combination of alefacept with other agents or monotherapy with other agents such as infliximab is the most effective treatment of psoriasis.

This is, to my knowledge, the first non-clinical trial related published report of the near total efficacy of the combination alefacept and nbUVB. The combination would appear a useful addition to the dermatologist's armamentarium in difficult to treat psoriasis. Although more trials and non-trial experience are needed to assess the optimal treatment for psoriatics, my report and those of others [2] offer new hope to patients with psoriasis.

References

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2. Stebbins WG, Lebwohl MG. Biologics in combination with nonbiologics: efficacy and safety. Dermatol Ther. 2004;17:432-40.

3. O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 2004;350:2591-602.

4. Amevive¨ (alefacept) package insert. Cambridge, Mass: Biogen, Inc. 2004.

5. Gordon KB, Sterry W. Efficacy of multiple courses of alefacept in combination with other psoriasis therapies: a study that reflects the clinical practice setting. J Am Acad Dermatol 2004:50;P152. Abstract P590.

6. Krueger GG, van de Kerkhof P. Safety of multiple courses of alefacept in combination with other psoriasis therapies: a study that reflects the clinical practice setting. J Am Acad Dermatol 2004:50;P152. Abstract P591.

7. van de Kerkhof, P., Griffiths C. Safety of multiple courses of alefacept in combination with other psoriasis therapies: a study that reflects the clinical practice setting. Poster presented at: 13th Congress of European Academy of Dermatology and Venereology (EADV); November 17-21, 2004. Florence Italy.

8. van de Kerkhof, P, Dubertret L. Efficacy of multiple courses of alefacept in combination with other psoriasis therapies: a study that reflects the clinical practice setting. Poster presented at: 13th Congress of European Academy of Dermatology and Venereology (EADV); November, 17-21 2004; Florence Italy.

9. Reich K, Wolff K, Berassinne MDL, Gottlieb AB, Langley R. Efficacy and safety of alefacept in psoriasis for whom convential therapies are ineffective or inappropriate. Poster presented at: 13th Congress of European Academy of Dermatology and Venereology (EADV); November 17-21, 2004.

10. Koo J, Rizova E, Freedman, D, Ortonne J-P. Combination therapy with alefacept and ultraviolet B light for treatment of psoriasis. J Am Acad Dermatol 2003:48;P156. Abstract 607.

11. Koo J. Combination therapy with alefacept and ultraviolet B light for treatment of psoriasis. Poster Presented at: International Psoriasis Symposium. June 18-22; New York, New York.

12. Ortonne JP, Khemis A. Combination therapy with alefacept plus narrowband ultraviolet B light for treatment of psoriasis. Poster Presented at: International Psoriasis Symposium. June 18-22; New York, New York.

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