NEW YORK — Increasing experience with the biologic agents in psoriatic arthritis is showing that these drugs are effective across all domains of this complex disease.
Tumor necrosis factor (TNF) inhibitors in particular have proven beneficial in the treatment of the peripheral arthritis, skin and nail disease, axial disease, dactylitis, and enthesitis associated with psoriatic arthritis (PsA).
Traditional disease-modifying antirheumatic drugs such as methotrexate, in contrast, may be useful for the arthritis and skin and nail disease, but are less effective for the other disease manifestations, according to Dr. Philip Mease, of the University of Washington, chief of rheumatology research, Swedish Medical Center, and head, Seattle Rheumatology Associates.
This difference in therapeutic efficacy may relate to important differences in pathophysiology between PsA and rheumatoid arthritis (RA).
For example, the synovitis in PsA is associated with less sublining infiltrate and with greater vascularity than in RA. There is also an increased expression of toll-like receptors 2 and 4 and an increased number of polymorphonuclear leukocytes, suggesting a greater role for the innate immune system and possibly microbial antigen stimulation, Dr. Mease said at a rheumatology meeting sponsored by New York University.
In PsA there also is a role for unique lineages of monocytes effector cells that differentiate into macrophages, osteoclasts, Langerhans cells, and dendritic cells via specific microenvironmental signals, he said.
Trials of anti-TNF drugs in PsA have permitted, but not required, both background methotrexate, nonsteroidal anti-inflammatories, and low-dose prednisone, and patients with oligoarticular disease have been included.
For infliximab, newly published 98-week data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) demonstrate a similar degree of sustained effectiveness.
In the open-label extension phase of the current trial, 62% of the 78 patients continuing on the drug at week 98 had achieved an American College of Rheumatology 20 (ACR20) response, while 45% and 35% had ACR50 and ACR70 responses, respectively.
Among those whose baseline PASI score was 2.5 or greater, 64% achieved a 75% improvement (J. Rheumatol., First Release March 15, 2008).
Similar results also have been seen with adalimumab, with 70% of patients reaching a PASI 75 response and improvements in disability being sustained out to week 48 (Arthritis Rheum. 2007;56:476–88).
For etanercept, 2-year data demonstrated sustained effectiveness in ACR scores over time and inhibition of progression of radiologic damage. Approximately 40% of patients achieved Psoriasis Area Severity Index (PASI) 75 responses (J. Rheumatol. 2006;33:712–21).
But unanswered questions remain regarding the use of anti-TNF drugs for PsA, such as whether additional benefits result from adding methotrexate, Dr. Mease said.
Because the trials thus far have been inconsistent as to whether background methotrexate was used, what is needed to answer this question is a trial that enrolls methotrexate-naive patients and randomizes them to methotrexate monotherapy, anti-TNF monotherapy, or the combination, he said.
“We also don't know what the impact of these drugs will be on PsA comorbidities,” he said.
RA registries are showing benefits in terms of cardiovascular outcomes, and this may also be the case in PsA. The answers will only come from sources such as the Consortium of Rheumatology Researchers of North America (CORRONA) database, which is collecting long-term data not only on outcomes in RA but also on PsA, osteoarthritis, and osteoporosis.
It also remains to be seen if other comorbidities associated with PsA will benefit from anti-TNF therapy, including infection, lymphoma, and depression.
“A further question is what we should do about patients who are inadequately responding to these anti-TNFs,” he said. A variety of other therapies are being assessed, including other anti-TNFs such as golimumab, intra-articular anti-TNF agents, other cytokine targets such as interleukin-12/interleukin-23, B-cell ablation with rituximab, and small molecules such as the JAK3 inhibitor.
Another new area of exploration in the spondylarthropathies is the use of anti-TNF drugs in preradiographic ankylosing spondylitis (AS), Dr. Mease noted.
In an open-label extension study of 22 patients with early axial spondylarthritis but without radiographic sacroiliitis, 46% of patients receiving adalimumab had a sustained 40% improvement in the Assessments in Ankylosing Spondylitis 40 (ASAS40) criteria (Ann. Rheum. Dis. 2007;66[suppl II]:64–5).
The impact of anti-TNF drugs on PsA comorbidities is unknown, but good CV outcomes are seen in RA registries. DR. MEASE