Successful rechallenge with anti–tumor necrosis factor α for psoriatic arthritis after development of demyelinating nervous system disease during initial treatment: Comment on the article by Mohan et al

Abstract

In the 2002 update of the American College of Rheumatology Guidelines for the Management of Rheumatoid Arthritis (1), the authors stress the need for antiplatelet therapy with low-dose aspirin for patients at risk for cardiovascular disease who are taking selective cyclooxygenase-2 (COX-2) agents, reasoning that, unlike nonselective nonsteroidal antiinflammatory drugs (NSAIDs), the selective COX-2 inhibitors have no effect on platelet adhesion or aggregation. This seems to imply that antiplatelet therapy with aspirin is required only when selective COX-2 inhibitors are used. I believe nonselective NSAIDs neither ensure appropriate antiplatelet prophylaxis, nor do they appear better than selective COX-2 inhibitors for patients at cardiovascular risk who are receiving concomitant aspirin antiplatelet therapy. Unlike the potent and irreversible inhibition of platelet COX-1 induced by aspirin, the antiplatelet effect of NSAIDs is highly variable and depends on two factors: their potency for inhibiting COX-1 at pharmacologic doses and their half-life (2). Thus, neither NSAIDs with a short half-life, such as ibuprofen, nor those with a relatively low COX-1 inhibitory effect, such as diclofenac, provide efficient and sustained antiplatelet therapy. Only drugs with a long half-life and a potent COX-1 inhibitory effect, such as indobufen, flurbiprofen, and naproxen, have been suggested to be potentially useful as antiplatelet agents (2). This may explain the observation of a higher rate of thrombotic events with rofecoxib than with naproxen in a large trial (3), something not observed when rofecoxib or celecoxib is compared with other nonselective NSAIDs (4,5). However, due to the reversibility of the antiplatelet effect of NSAIDs, the cardioprotective effect of these drugs as shown in clinical trials, where compliance with the dose and treatment schedule is usually better, does not necessarily apply to clinical practice, where intermittent use by patients is common. Accordingly, epidemiologic studies have failed to demonstrate cardioprotective effects of NSAIDs, in contrast with aspirin (6). Furthermore, recently published data demonstrate that in patients taking aspirin, ibuprofen antagonizes the irreversible platelet inhibition induced by aspirin, whereas other drugs with lower COX-1 inhibitory effects, such as diclofenac or rofecoxib, do not interfere with aspirin's effects (7). An additional matter of concern when using aspirin with NSAIDs is their synergistic action in terms of gastrointestinal toxicity, something that has not been sufficiently evaluated for COX-2 selective drugs (8). In conclusion, neither relying on the antiplatelet effect of NSAIDs in patients at cardiovascular risk, nor using NSAIDs instead of selective COX-2 inhibitors when low-dose aspirin is needed, can be recommended based on available evidence.

Tumor necrosis factor‐α antagonists and neuropathy

“…Conceivably, lower drug doses could effectively treat the underlying inflammatory disease without altering the immune system enough to elicit a neuropathy. 11 …”

“…After IVIg, the patient recovered fully by 3 weeks, and was subsequently successfully rechallenged with lower dose infliximab at 3-month intervals. 11 With such limited reporting, no definitive conclusion can be drawn about the safety of TNF-␣-blocker rechallenge once patients develop a neuropathy. Conceivably, lower drug doses could effectively treat the underlying inflammatory disease without altering the immune system enough to elicit a neuropathy.…”

Neuropathy resembling CIDP in patients receiving tumor necrosis factor-α blockers

“…This was a recurrence of Guillain-Barré syndrome, but the authors suggest a natural recurrence rather than the direct implication of anti-TNF␣. 9 CIDP is an acquired demyelinating disease of the peripheral nerves in which myelin is presumably the target of the immune attack. Our cases could be the result of a specific autoimmune response induced by anti-TNF␣.…”

Etanercept and demyelinating disease in a patient with psoriasis

“…Case reports of successful rechallenges with TNF-a antagonists exist. 39 It is impossible to rule in or rule out a cause-and-effect relationship, given the nature of MS as a waxing and waning disease as well as the abundance of data suggesting a relationship between demyelinating disease and the TNF-a pathway. A question that remains unanswered pending future studies is whether the TNF-a antagonist therapy truly increases the risk of demyelinating disease or are the reported cases the background incidence of MS in a population receiving more careful medical follow-up.…”