SNOWMASS, COLO. — Long-term adherence to anti–tumor necrosis factor agents appears to be better—and rates of malignancy and serious infection lower—in patients who are treated for ankylosing spondylitis than in those with rheumatoid arthritis or some of the other rheumatic conditions for which the drugs are indicated.
Another major distinction between ankylosing spondylitis (AS) patients and those with other rheumatic diseases in terms of anti-TNF response is that rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients are significantly more likely to remain on treatment long term if they're on concomitant methotrexate, whereas AS patients' unequalled adherence to anti-TNF therapy is not affected by whether or not they're also on methotrexate, Dr. Robert D. Inman said at a symposium sponsored by the American College of Rheumatology.
These observations come from the Norwegian Disease-Modifying Antirheumatic Drug (NOR-DMARD) registry. The Norse study also demonstrated that AS patients were an adjusted 34% less likely than those with RA to terminate therapy with infliximab (Remicade), etanercept (Enbrel), or adalimumab (Humira) during the first year after starting their biologic. The PsA group was 24% less likely than RA patients to discontinue anti-TNF therapy within a year (Arthritis Rheum. 2008;59:234–40).
The reasons cited for discontinuing anti-TNF therapy varied according to disease category. Lack of efficacy was cited as the primary reason by only 18% of PsA patients who quit, compared with 36% of those with AS and 39% of RA patients. Adverse events were cited as the reason for stopping treatment by 69% of PsA patients who discontinued therapy, compared with 44% of those with AS and 49% of RA patients.
The particularly favorable risk:benefit ratio for anti-TNF therapy in AS patients was highlighted in a recent analysis of data on more than 19,000 adalimumab-treated patients in 36 clinical trials that were conducted over a 10-year period. Adalimumab-treated AS patients had rates of malignancy and serious infections as low as or lower than those in patients with the five other immune-mediated inflammatory diseases for which the biologic agent is indicated, said Dr. Inman, professor of medicine and immunology at the University of Toronto.
For example, the rate of tuberculosis and other serious infections was 1.11 per 100 patient-years in AS patients, compared with 4.65 per 100 patient-years in RA patients, 5.18 in those with Crohn's disease, 2.81 in PsA patients, 2.76 in those with juvenile idiopathic arthritis, and 1.32 per 100 patient-years for psoriasis patients.
The incidence of malignancies other than lymphoma and nonmelanoma skin cancer was greatest in the RA population on adalimumab (0.76 cases per 100 patient-years vs. 0.08 per 100 patient-years in the AS group). Patients with RA also had the highest rate of nonmelanoma skin cancer and the second-highest lymphoma rate of the six autoimmune inflammatory diseases for which adalimumab is approved.
As for the relative efficacy of the various anti-TNF drugs in the setting of AS, there is a dearth of head-to-head comparative studies. However, scrutiny of the various placebo-controlled, randomized trials suggests that the efficacy of various agents in AS “looks very comparable,” with 51%–61% of patients on etanercept, infliximab, adalimumab, or golimumab showing a 20% improvement in ASAS 20 (Assessment in Ankylosing Spondylitis 20) at 24 weeks, according to Dr. Inman.
Disclosures: Dr. Inman disclosed serving as a consultant to Sanofi-Aventis, Amgen Inc., Wyeth, Abbott Laboratories, Schering-Plough Corp., and Centocor Inc.