The Latest on Treating Psoriatic Arthritis
The Latest on Treating Psoriatic Arthritis
Recently, apremilast (Otezla®) was approved for both psoriasis and for PsA. Apremilast is a small-molecular agent administered orally that inhibits phosphodiesterase 4 (PDE-4) and thereby inhibits inflammatory pathways. It is of some interest that PDE-4 is downstream from TNF in the inflammatory cascade, although such pathways tend to show extensive cross-talk.
Apremilast demonstrated good efficacy in clinical trials in both psoriasis and PsA. For the latter disease, in several randomized trials, American College of Rheumatology 20% improvement (ACR20) responses of 32%-41% were seen, vs 18%-19% for placebo—a statistically significant difference.
Apremilast is dosed at 30 mg twice daily, with an initial slow step-up. Its safety and tolerability appear to be good, with only limited need for laboratory monitoring. Nausea, diarrhea, and headache are common adverse events, especially during the first 2 weeks of treatment. Apremilast may increase the risk for depression and involuntary weight loss.
Ustekinumab (Stelara®) is a human monoclonal antibody that specifically binds a chain that is shared by both IL-12 and IL-23, thereby neutralizing the activity of both signaling molecules—the latter being considered the more important one in PsA. Ustekinumab is administered subcutaneously at 45-90 mg every 12 weeks (with starter doses at 0 and 4 weeks) and was approved in 2010 for the treatment of psoriasis.
Because of impressive clinical efficacy, including a trial demonstrating superiority compared with etanercept, and its good safety profile, ustekinumab has been used increasingly in this disease. More recently, ustekinumab was also approved for the treatment of PsA, on the basis of several randomized trials that demonstrated an efficacy significantly greater than that of placebo. The absolute magnitude of responses in these trials was somewhat less than has historically been the case with anti-TNF biologics, but no direct comparisons have been done. There is an impression among many clinicians that ustekinumab, despite its excellent efficacy against psoriasis in the skin, is only moderately effective for inflammation in the joints, tendons, and other areas.
Common adverse events in trials with ustekinumab included various infections, but there was no clearly identified increased risk compared with placebo. Screening for tuberculosis was mandatory in trials of ustekinumab, but it is not known whether there is an increased risk for reactivation of tuberculosis.
New Agents for PsA
Apremilast Approved
Recently, apremilast (Otezla®) was approved for both psoriasis and for PsA. Apremilast is a small-molecular agent administered orally that inhibits phosphodiesterase 4 (PDE-4) and thereby inhibits inflammatory pathways. It is of some interest that PDE-4 is downstream from TNF in the inflammatory cascade, although such pathways tend to show extensive cross-talk.
Apremilast demonstrated good efficacy in clinical trials in both psoriasis and PsA. For the latter disease, in several randomized trials, American College of Rheumatology 20% improvement (ACR20) responses of 32%-41% were seen, vs 18%-19% for placebo—a statistically significant difference.
Apremilast is dosed at 30 mg twice daily, with an initial slow step-up. Its safety and tolerability appear to be good, with only limited need for laboratory monitoring. Nausea, diarrhea, and headache are common adverse events, especially during the first 2 weeks of treatment. Apremilast may increase the risk for depression and involuntary weight loss.
Ustekinumab
Ustekinumab (Stelara®) is a human monoclonal antibody that specifically binds a chain that is shared by both IL-12 and IL-23, thereby neutralizing the activity of both signaling molecules—the latter being considered the more important one in PsA. Ustekinumab is administered subcutaneously at 45-90 mg every 12 weeks (with starter doses at 0 and 4 weeks) and was approved in 2010 for the treatment of psoriasis.
Because of impressive clinical efficacy, including a trial demonstrating superiority compared with etanercept, and its good safety profile, ustekinumab has been used increasingly in this disease. More recently, ustekinumab was also approved for the treatment of PsA, on the basis of several randomized trials that demonstrated an efficacy significantly greater than that of placebo. The absolute magnitude of responses in these trials was somewhat less than has historically been the case with anti-TNF biologics, but no direct comparisons have been done. There is an impression among many clinicians that ustekinumab, despite its excellent efficacy against psoriasis in the skin, is only moderately effective for inflammation in the joints, tendons, and other areas.
Common adverse events in trials with ustekinumab included various infections, but there was no clearly identified increased risk compared with placebo. Screening for tuberculosis was mandatory in trials of ustekinumab, but it is not known whether there is an increased risk for reactivation of tuberculosis.
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