Exploring Off-Label Use of Biologics for Dermatologic Indications

Exploring Off-Label Use of Biologics for Dermatologic Indications Although dermatologists often think of biologics in terms of treating psoriasis, they can treat a variety of other skin diseases.

By Jerry Bagel, MD

ermatologists’ primary inter- amounts of adalimumab are effective Another disease that efalizumab est in biologics is mostly lim- after the initial clearing from the first often treats effectively is discoid lupus. Dited to the treatment of psori- treatment of two to six months. In another small case report reported at asis and psoriatic arthritis. While Etanercept (Enbrel, Amgen-Wyeth) the poster sessions at the recent AAD many of the biologics are much need- has also been used to treat hidradenitis conference, five patients with refractory ed, highly successful treatments for suppurativa.3 In one case study, six discoid lupus all responded very well to psoriatic disease, there is a wide assort- patients were treated with etanercept efalizumab treatment. Although much ment of other dermatologic diseases therapy 25mg sq two times a week for research is needed concerning the possi- and disorders that can be treated suc- 24 weeks. Results showed that etaner- ble treatment of discoid lupus, this pre- cessfully with biologics. Many of these cept was relatively effective. It should liminary report elucidates another pos- conditions are more rare than psoria- also be noted that all patients rated sible benefit of off-label use of efal- sis, but it is important for physicians etanercept as the most effective treat- izumab. to consider off-label uses of biologics ment they have received to date. A It has also been shown that another for such conditions, since they often recent notable study found that rare skin condition, lupus pernio, can are highly efficacious. patients that haven’t responded to be treated effectively with infliximab. Following are brief accounts of bio- isotretinoin did extremely well with Results of a recent study suggest that logics treating dermatologic disease efalizumab therapy, improving after patients with more severe disease tend- effectively. It should be noted that many just one month of treatment (Poster). ed to benefit more from infliximab of these case reports represent prelimi- Another rare disease that efalizumab treatment. Interestingly, patients in nary findings and represent a growing (Raptiva, Genentech) has been shown both arms responded very well to body of data suggesting that biologics to treat effectively is pityriasis rubra infliximab treatment, resulting in statis- can be used to treat many dermatologic pilaris (PRP). Although treating PRP is tically significant improvement.5 disorders with varying success. difficult because it responds somewhat In cases of lichen planus, efalizumab poorly, efalizumab may actually yield a may be effective based on one case Rare Off-Label Uses response. In one recently reported report. Four patients with the disease Last year, two case reports were pub- study presented at poster sessions at all experienced at least a 50 percent lished1-2 regarding the treatment of the recent American Academy of reduction of the disease on efalizumab hidradenitis suppurativa with adali- Dermatology Annual Meeting, patients therapy. On average, there was a 71 mumab. Patients were treated with responded to 1mg/kg of efalizumab per percent improvement of the disease for 40mg of adalimumab (Humira, week within three months. By six patients receiving efalizumab.6 Abbott) every other week for varying months of treatment, many patients In pyoderma gangrenosum (PG), degrees of hidradenitis suppurativa, were completely cleared and remained the largest study I have observed which resulted in clearing within two clear for 20 months. Another study involved 13 patients with inflammatory to six months. Sometimes, in order to involving patients with PRP who were bowel disease and PG who were treated maintain clearance, increasing adali- treated with infliximab (Remicade, with infliximab.7 Ten patients respond- mumab treatment to 40mg every week Centocor) 5mg/kg four weeks apart. ed well and maintained healing with may be necessary if the disease persists. All three patients achieved marked infusions every four to 12 weeks, and But reports indicate that if hidradenitis response within two weeks with no most patients were able to discontinue suppurativa is persistent, decreased adverse events.4 systemic steroids. One case report doc-

56 Practical Dermatology April 2007

[ Psoriasis Update]

AD Management Another more prominent dermatologic disorder that typically responds well to “Another more biologics is atopic dermatitis. Though prominent most cases of AD are treated with topical agents, severe cases often require more dermatologic rigorous treatment, and in such cases efalizumab has been shown to be some- disorder that what efficacious. In a recent study, efal- typically responds well izumab therapy resulted in significant clinical improvements in six out of ten to biologics is atopic patients with severe AD, showing that efalizumab may be a viable alternative to dermatitis. Though current systemic immunosuppresants.11

most cases of AD 1. Moul DK, et al. “The cutting edge. Severe hidradenitis suppurativa treated with adalimumab.” Arch Dermatol. 2006 Sep; 142(9): 1110-2 2. Sheinfeld M. “Treatment of coincident seronegative arthritis and hidraden- are treated tis supprativa with adalimumab.” J Am Acad Dermatol. 2006 Jul; 55(1):163-4 with topical agents, 3. Cusack C, Buckley C. “Etanercept: effective in the management of hidradenitis suppurativa.” British Journal of Derm. 2006. Apr; 154(4): 726-9 severe cases often 4. Drosou A. “Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses.” Journal of Cutaneous Medicine and Surgery, 2003. Sep-Oct; 7(5): 382-6. require more rigorous 5. Baughman RP, et al. “Infliximab therapy in patients with chronic sar- coidosis and pulmonary involvement.” Am J Respir Crit Care Med. 2006 Oct treatment.” 1; 174(7): 795-802. 6. Cheng A, et al. “Oral erosive lichen planus treated with efalizumab.” Arch Dermatol. 2006 Jun; 142(6): 680-2. 7. Regueiro M, et al. “Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease.” American Journal of Gastroentorology. 2003. Aug; 98(8): 1821-6. uments successful treatment of PG not nearly as effective with genital 8. Graves J, et al. “Off-label uses of biologics in dermatology: rituximab, 10 omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept with adalimumab in which patients ulcers. Although this is another poten- (part 2 of 2).” JAAD Jan 2007. 56(1): e55-79. were given 80mg/kg for the first two tial therapeutic approach, there have 9. Connolly M, et al. “Infliximab treatment for severe orogenital ulceration weeks followed by 40 mg weekly. All been cases of failure of TNF inhibitors in Behcet's disease.” British J Dermatol. 2005. Nov;153(5):1073-5. 10. Melikoglu M, et al. “Short-term trial of etanercept in Behcet's disease: patients achieved complete healing as well. a double blind, placebo controlled study.” J Rheumatol. 2005 within five and a half months.8 Jan;32(1):98-105. 11. Takiguchi R et al. “Efalizumab for severe atopic dermatitis: a pilot study Finally, some biologics can poten- in adults. J Am Acad Dermatol.” 2007 Feb; 56(2): 222-7. tially treat Bechet’s Disease. In one case report, patients treated with infliximab (3 or 5mg/kg) had complete remission within one month. In Your Practice Clearance is typically main- New tained with infusions every four to eight weeks.9 Bechet’s disease Half a Man. According to data presented at the 65th Annual Meeting of Dermatology, drivers who spend a signifi- has also been treated with etancercept. In one study with cant amount of time in their cars may be at greater risk of skin cancer—the risk is especially notable in men and on etanercept, 40 patients showed the left side of the body. A total of 898 patients with skin cancer occurring on either side of the body were enrolled significant improvement tak- in a retrospective chart review showing that of the 53 percent of left-sided skin cancers, nearly two thirds of these ing 25mg sq twice-weekly. cases were found in men. Forty-five percent of patients maintained complete remis- Rewriting the Alphabet. According to a study in Archives of Dermatology (Dec. 2006), melanomas that are sion of oral ulcers as opposed growing rapidly do not fit the ABCD rule for melanoma. They are thicker, symmetrical, have regular borders, and often to five percent placebo. itch or bleed. Observing 404 melanoma patients, researchers concluded that one third of the melanomas grew However, this treatment is 0.5mm per month or more. These fast-growing tumors were often observed to lack melanin.

58 Practical Dermatology April 2007