LAS VEGAS – Emerging data support the practice of switching biologic agents after an initial biologic therapy fails in psoriasis, and even the possibility of rotating back to a biologic that didn’t work previously, according to Dr. Francisco Kerdel, director of the dermatology inpatient service at the University of Miami Hospital.
In one recent series of 747 psoriasis patients on biologics, the 4-year drug response was in the range of 40% for etanercept or adalimumab and 70% for infliximab ( Br. J. Dermatol. 2011;164:1091-6 ). "Thus, there is a logical need for ‘switching’ [biologic] therapy," he noted at the SDEF Las Vegas Dermatology Seminar.
The reasons for treatment failure are not known. Antibody production has been suspected of playing a role, but the presence of antibodies seldom correlates with clinical response, he said.
In a 16-week, open-label trial, a Physician Global Assessment (PGA) rating of "clear" or "minimal" was achieved in 52% of 152 patients who had chronic plaque psoriasis and were switched to adalimumab following suboptimal responses to etanercept, methotrexate, or phototherapy ( J. Am. Acad. Dermatol. 2011;64:671-81 ).
In the PSUNRISE study (a prospective, multicenter, open-label study of infliximab treatment in 215 patients with plaque psoriasis who had had a prior inadequate response to etanercept), a PGA score of 0 (clear) or 1 was achieved by week 10 in 65% of the 179 completers, and 60% remained at PGA 0-1 in weeks 14-26. These data have been submitted for publication, according to Dr. Kerdel, who was one of the study authors.
Good to excellent responses were achieved with ustekinumab at doses of either 45 mg or 90 mg, depending on body weight, in 9 of 11 psoriasis patients who had experienced treatment failures on multiple biologics, including infliximab (11 patients), etanercept (10), efalizumab (9), adalimumab (7), and golimumab (3) ( Int. J. Dermatol. 2011;50:478-82 ).
There is even some evidence that patients can return with success to a biologic therapy that they had previously failed.
Dr. Kerdel and his associates have conducted an open-label study of etanercept re-treatment in 20 patients with moderate to severe psoriasis (defined as a PGA score of 3 or greater) who had had prior therapy with etanercept for a minimum of 6 months but had discontinued it because of loss of efficacy. The 10 men and 10 women had an average age of 49 years, with an average of 3.5 years between stopping and restarting etanercept. Five patients withdrew and were classified as treatment failures, regardless of the reason for withdrawal.
The proportion of responders (defined as those achieving a PGA score of 0 or 1) was 5 of 20 (25%) at week 8, and 8 of 20 (40%) at week 12. Body weight appeared to play a role. Among the 14 patients who had a PGA score of 2 or less at week 12, the average weight was 198.4 pounds, compared with 217.6 pounds for the 6 who did not have that response.
These preliminary findings suggest that rotational therapy is possible, at least in cases of secondary failure with etanercept. Rotational therapy may be possible with other biologics as well, but further studies are necessary, Dr. Kerdel concluded.
It had been thought that this practice would be of limited value because of the development of circulating antibodies, which were found in one study to range in prevalence from 5% of rheumatoid arthritis patients on ustekinumab to 87% of those treated with adalimumab ( Clin. Rev. Allergy Immunol. 2010;38:82-9 ). However, the therapeutic relevance of non-neutralizing vs. neutralizing antibodies is currently unknown, he said.
In a recent prospective cohort study of 272 RA patients treated with adalimumab, 28% had developed antiadalimumab antibodies, which appeared within the first 28 weeks of treatment in two-thirds of them. Over 3 years of follow-up, 38% of the patients with antibodies discontinued adalimumab therapy because of treatment failure, compared with 14% of those who did not develop antibodies. Minimal disease activity was achieved in 48% without antibodies, compared with 13% who had antibodies ( JAMA 2011;305:1460-8 ).
And in a retrospective observational study of 97 psoriasis patients who had been treated with anti–tumor necrosis factor–alpha therapy (60 on a first agent, 22 having failed one agent, 9 having failed two agents, and 6 having failed all three agents), antinuclear antibodies developed in 17%, 54%, 78% and 83%, respectively ( Br. J. Dermatol. 2010;162:780-5 ). "So, antibodies do seem to play a role" in treatment failure, Dr. Kerdel commented.
Dr. Kerdel disclosed that he has been involved in clinical studies, has participated in advisory boards, and is a speaker for Amgen, Abbott, Janssen, Genentech, Astellas, Stiefel, Pfizer, Merck, Novartis, Eisai, and Celgene. SDEF and this news organization are owned by Elsevier.