OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 10 February 2018

• Zimmerman HJ. Drugs used to treat rheumatic and musculospastic disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 517-54.

  (Expert review of hepatotoxicity published in 1999, well before the availability of most monoclonal antibody therapies).
• Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 569-91.

  (Review of hepatotoxicity of immunosuppressive agents mentions rituximab and problems of reactivation of hepatitis B, but also states that "the biological immunosuppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists"; efalizumab not specifically mentioned).
• Krensky AM, Vincenti F, Bennett WM. Immunomodulators. In, Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006, pp. 1405-88.

  (Textbook of pharmacology and therapeutics).
• Efalizumab (Raptiva) for treatment of psoriasis. Med Lett Drugs Ther 2003; 45 (1171): 97-8. [PubMed: 14657802]

  (Concise summary of efficacy, safety and costs of efalizumab shortly after its approval for use in psoriasis in the US; no mention of ALT elevations or hepatotoxicity).
• Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH, Walicke P, et al.; Efalizumab Study Group. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 2003; 349: 004-13. [PubMed: 14627785]

  (Among 597 patients with psoriasis treated with efalizumab [1 or 2 mg/kg/week] or placebo for 12-24 weeks, clinical responses were more frequent with efalizumab [22% and 28% vs 5% at week 12] as were side effects including headaches, chills, fever, nausea, myalgias, and acne; Alk P and GGT levels were slightly and transiently elevated, but there were “no other notable changes” in laboratory values).
• Dubertret L, Sterry W, Bos JD, Chimenti S, Shumack S, Larsen CG, Shear NH, Papp KA; CLEAR Multinational Study Group. Clinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial. Br J Dermatol 2006; 155: 170-81. [PubMed: 16792770]

  (Among 793 patients with psoriasis treated with efalizumab or placebo for 12 weeks, Alk P levels increased by ~3 U/L by week 12, but abnormalities of ALT and AST "were generally similar to those present at baseline").
• Papp KA, Bressinck R, Fretzin S, Goffe B, Kempers S, Gordon KB, Caro I, et al.; Efalizumab Study Group. Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: a phase IIIb, randomized, controlled trial. Int J Dermatol 2006; 45: 605-14. [PubMed: 16700803]

  (Among 686 patients with psoriasis who received efalizumab [0.7 mg/kg initially and then 1 mg/kg weekly] or placebo for 12 weeks, there were "no clinically significant changes in... laboratory parameters and no evidence of end-organ toxicities"; there was a slight increase in Alk P levels but no change in ALT or AST values).
• Gordon KB, Papp KA, Hamilton TK, Walicke PA, Dummer W, Li N, Bresnahan BW, Menter A; Efalizumab Study Group. Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA 2003; 290: 3073-80. [PubMed: 14679270]

  (Among 556 patients with psoriasis treated with efalizumab or placebo for 12 weeks, response rates were 24% on efalizumab vs 4% of placebo, and therapy was "safe and well tolerated" with "no clinically significant laboratory abnormalities").
• Kaiser T, Moessner J, Patel K, McHutchison JG, Tillmann HL. Life threatening liver disease during treatment with monoclonal antibodies. BMJ 2009; 338: b508. [PubMed: 19224957]

  (66 year old man with psoriasis was treated with efalizumab [anti-CD11a] and then adalimumab [anti-TNF], and 11 days later developed jaundice and severe hepatitis [bilirubin 9.1 rising to 52 mg/dL, ALT 549 U/L, Alk P 131 U/L], with HBsAg being detected and slow but eventual recovery).
• Primo J, Michavila J, Jiménez I. [Efalizumab-induced autoimmune hepatitis]. Gastroenterol Hepatol 2010 Jan; 33 (1): 69-70. Spanish. [PubMed: 19800148]

  (55 year old woman with psoriasis developed serum enzyme elevations after 9 doses of efalizumab [50 mg weekly], with bilirubin normal, but ALT 235 U/L, Alk P 428 U/L, ANA rising to 1:1,280 which persisted for 6 months despite stopping therapy, ultimately responding to corticosteroid and azathioprine therapy).
• Gadzia J, Turner J. Progressive multifocal leukoencephalopathy in two psoriasis patients treated with efalizumab. J Drugs Dermatol 2010; 9: 1005-9. [PubMed: 20684152]

  (Two patients, 70 and 73 year old, man and woman, treated for psoriasis with efalizumab for more than 3 years developed progressive neurologic deficits and had JC virus found in spinal fluid compatible with diagnosis of progressive multifocal leukoencephalopathy [PMLE], dying shortly after diagnosis).
• Kothary N, Diak IL, Brinker A, Bezabeh S, Avigan M, Dal Pan G. Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients. J Am Acad Dermatol 2011; 65: 546-51. [PubMed: 21514689]

  (Analysis of 3 cases of PMLE associated with efalizumab therapy of psoriasis from the FDA Adverse Event Reporting System, 2 men and 1 woman, ages 43-73 on efalizumab for 3 to 4 years, presenting with vertigo, ataxia, paraesthesias and progressive neurologic course, dying 2-6 months after presentation).
• Aithal GP. Hepatotoxicity related to antirheumatic drugs. Nat Rev Rheumatol 2011; 7: 139-50. [PubMed: 21263458]

  (Analysis of spontaneous adverse event reporting of progressive PMLE in the US between 2004-2010 identified 635 cases with higher than expected number of cases from several immunosuppressive monoclonal antibodies, including efalizumab [n=12], rituximab [124] and natalizumab [123]).
• Rustin MH. Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data. Br J Dermatol 2012; 167 Suppl 3: 3-11. [PubMed: 23082810]

  (Analysis of long term severe adverse events associated with use of biologic agents for psoriasis: "with the exception of efalizumab,..., these biologics are generally well tolerated in long-term studies").
• Badavanis G, Pasmatzi E, Monastirli A, Tsambaos D. Biologic agents in systemic dermatotherapy: cutaneous and systemic side effects. Curr Drug Saf 2017 May 18. [Epub ahead of print] [PubMed: 28521707]

  (Review of the systemic side effects of biologic agents used to treat psoriasis after the withdrawal of efalizumab because of a concern over its serious and fatal side effects).