Options exist for psoriasis patients with multiple anti-TNF failures

LAS VEGAS – The use of an alternative anti–tumor necrosis factor drug is not necessarily precluded in a psoriasis patient with both skin and joint symptoms who has failed two previous anti-TNF drugs, according to Dr. Kenneth B. Gordon.

Dr. Gordon, professor of dermatology at Northwestern University, Chicago, described a case involving a 52-year-old man with a 20-year history of psoriasis who initially presented with mainly scalp and limited plaque psoriasis, and who was treated with topical corticosteroids and topical calcipotriene. After developing more extensive disease, he was treated successfully with ultraviolet B phototherapy.

Eleven years after first presenting with psoriasis, he presented with peripheral arthritis and enthesitis and was diagnosed with psoriatic arthritis.

The patient was treated initially with sulfasalazine, but failed to respond; methotrexate had only modest benefit, and at higher doses the patient developed liver function test abnormalities due to steatohepatitis, Dr. Gordon said at Perspectives in Rheumatic Diseases 2013.

Etanercept was initiated at 50 mg twice weekly, and the patient had an excellent initial response.

However, after stepping down to 50 mg weekly, his psoriasis flared.

"His joints were doing fine, but his skin was getting bad," Dr. Gordon said, noting that this type of response was also seen in early studies of etanercept, which showed that when doses were reduced to 50 mg weekly after 12 weeks, responses leveled off, with some patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) 75 response, and some losing PASI 75 response.

"It turns out that this occurs in 20%-30% of patients," he said, adding that some controversy exists regarding dosing, because "it’s not entirely clear that if you had just started at the lower dose and just let them go at the 50 mg once a week, that at 6 months they’d be any different than if you gave them the higher dose initially."

The REVEAL study of adalimumab for psoriasis also demonstrated loss of response after 33 weeks among those with an initial PASI 75 response (J. Am. Acad. Dermatol. 2012;66:241-51), he said.

"So clearly, patients lose response. Now, that lessens over time, but in the first year in psoriasis – and my guess is, in psoriatic arthritis as well – you have loss of effect at a relatively high level with all of these medicines," he said.

In fact, in the patient Dr. Gordon presented, a switch to adalimumab at a dose of 40 mg every other week resulted in an excellent initial response in both joints and skin, but skin symptoms returned after 8 months.

"This is something we’re all familiar with – patients doing well on an anti-TNF and then losing effect after a period of time on medication," he said.

So what are the alternatives?

An anti-TNF drug option after the patient cycles through etanercept, adalimumab, and infliximab is certolizumab, which was approved in September for the treatment of psoriatic arthritis. Study data suggest that the drug is "quite effective for psoriasis, was well tolerated, and similar to the other anti-TNFs," he said.

Using certolizumab is a reasonable approach that appears to work for both skin and joint symptoms, he said.

Golimumab is another possible option for treatment, but primary psoriasis data are lacking with this drug.

"It is my feeling that golimumab is probably not as potent for psoriasis as the other anti-TNF agents that we have, but that is an opinion," he said.

As for alternatives to anti-TNF agents, the PHEONIX 2 trial (Lancet 2008;371:1675-84) provided reasonable data in support of the interleukin-12 and -23 monoclonal antibody ustekinumab for skin disease, but patients who failed prior anti-TNF therapy actually had a poorer outcome, so that is something to keep in mind, he said, noting that adding methotrexate may help prevent a flare in patients who are switched from an anti-TNF agent to ustekinumab.

Ustekinumab, which also was approved in September for the treatment of psoriatic arthritis, is likely more useful for the skin, but is not exceptional for joint disease, he said at the meeting, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Apremilast and tofacitinib, drugs now in development for psoriasis, may also prove useful in the future, as they may "theoretically be of benefit" based on currently available data, he said.

Dr. Gordon has received research support and/or honoraria from AbbVie (which markets adalimumab), Amgen (which markets etanercept), Celgene (which is developing apremilast), Eli Lilly, Janssen (which markets golimumab, infliximab, and ustekinumab), Novartis, and Pfizer (which markets tofacitinib).

LAS VEGAS – The use of an alternative anti–tumor necrosis factor drug is not necessarily precluded in a psoriasis patient with both skin and joint symptoms who has failed two previous anti-TNF drugs, according to Dr. Kenneth B. Gordon.

Dr. Gordon, professor of dermatology at Northwestern University, Chicago, described a case involving a 52-year-old man with a 20-year history of psoriasis who initially presented with mainly scalp and limited plaque psoriasis, and who was treated with topical corticosteroids and topical calcipotriene. After developing more extensive disease, he was treated successfully with ultraviolet B phototherapy.

Eleven years after first presenting with psoriasis, he presented with peripheral arthritis and enthesitis and was diagnosed with psoriatic arthritis.

The patient was treated initially with sulfasalazine, but failed to respond; methotrexate had only modest benefit, and at higher doses the patient developed liver function test abnormalities due to steatohepatitis, Dr. Gordon said at Perspectives in Rheumatic Diseases 2013.

Etanercept was initiated at 50 mg twice weekly, and the patient had an excellent initial response.

However, after stepping down to 50 mg weekly, his psoriasis flared.

"His joints were doing fine, but his skin was getting bad," Dr. Gordon said, noting that this type of response was also seen in early studies of etanercept, which showed that when doses were reduced to 50 mg weekly after 12 weeks, responses leveled off, with some patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) 75 response, and some losing PASI 75 response.

"It turns out that this occurs in 20%-30% of patients," he said, adding that some controversy exists regarding dosing, because "it’s not entirely clear that if you had just started at the lower dose and just let them go at the 50 mg once a week, that at 6 months they’d be any different than if you gave them the higher dose initially."

The REVEAL study of adalimumab for psoriasis also demonstrated loss of response after 33 weeks among those with an initial PASI 75 response (J. Am. Acad. Dermatol. 2012;66:241-51), he said.

"So clearly, patients lose response. Now, that lessens over time, but in the first year in psoriasis – and my guess is, in psoriatic arthritis as well – you have loss of effect at a relatively high level with all of these medicines," he said.

In fact, in the patient Dr. Gordon presented, a switch to adalimumab at a dose of 40 mg every other week resulted in an excellent initial response in both joints and skin, but skin symptoms returned after 8 months.

"This is something we’re all familiar with – patients doing well on an anti-TNF and then losing effect after a period of time on medication," he said.

So what are the alternatives?

An anti-TNF drug option after the patient cycles through etanercept, adalimumab, and infliximab is certolizumab, which was approved in September for the treatment of psoriatic arthritis. Study data suggest that the drug is "quite effective for psoriasis, was well tolerated, and similar to the other anti-TNFs," he said.

Using certolizumab is a reasonable approach that appears to work for both skin and joint symptoms, he said.

Golimumab is another possible option for treatment, but primary psoriasis data are lacking with this drug.

"It is my feeling that golimumab is probably not as potent for psoriasis as the other anti-TNF agents that we have, but that is an opinion," he said.

As for alternatives to anti-TNF agents, the PHEONIX 2 trial (Lancet 2008;371:1675-84) provided reasonable data in support of the interleukin-12 and -23 monoclonal antibody ustekinumab for skin disease, but patients who failed prior anti-TNF therapy actually had a poorer outcome, so that is something to keep in mind, he said, noting that adding methotrexate may help prevent a flare in patients who are switched from an anti-TNF agent to ustekinumab.

Ustekinumab, which also was approved in September for the treatment of psoriatic arthritis, is likely more useful for the skin, but is not exceptional for joint disease, he said at the meeting, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Apremilast and tofacitinib, drugs now in development for psoriasis, may also prove useful in the future, as they may "theoretically be of benefit" based on currently available data, he said.

Dr. Gordon has received research support and/or honoraria from AbbVie (which markets adalimumab), Amgen (which markets etanercept), Celgene (which is developing apremilast), Eli Lilly, Janssen (which markets golimumab, infliximab, and ustekinumab), Novartis, and Pfizer (which markets tofacitinib).

LAS VEGAS – The use of an alternative anti–tumor necrosis factor drug is not necessarily precluded in a psoriasis patient with both skin and joint symptoms who has failed two previous anti-TNF drugs, according to Dr. Kenneth B. Gordon.

Dr. Gordon, professor of dermatology at Northwestern University, Chicago, described a case involving a 52-year-old man with a 20-year history of psoriasis who initially presented with mainly scalp and limited plaque psoriasis, and who was treated with topical corticosteroids and topical calcipotriene. After developing more extensive disease, he was treated successfully with ultraviolet B phototherapy.

Eleven years after first presenting with psoriasis, he presented with peripheral arthritis and enthesitis and was diagnosed with psoriatic arthritis.

The patient was treated initially with sulfasalazine, but failed to respond; methotrexate had only modest benefit, and at higher doses the patient developed liver function test abnormalities due to steatohepatitis, Dr. Gordon said at Perspectives in Rheumatic Diseases 2013.

Etanercept was initiated at 50 mg twice weekly, and the patient had an excellent initial response.

However, after stepping down to 50 mg weekly, his psoriasis flared.

"His joints were doing fine, but his skin was getting bad," Dr. Gordon said, noting that this type of response was also seen in early studies of etanercept, which showed that when doses were reduced to 50 mg weekly after 12 weeks, responses leveled off, with some patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) 75 response, and some losing PASI 75 response.

"It turns out that this occurs in 20%-30% of patients," he said, adding that some controversy exists regarding dosing, because "it’s not entirely clear that if you had just started at the lower dose and just let them go at the 50 mg once a week, that at 6 months they’d be any different than if you gave them the higher dose initially."

The REVEAL study of adalimumab for psoriasis also demonstrated loss of response after 33 weeks among those with an initial PASI 75 response (J. Am. Acad. Dermatol. 2012;66:241-51), he said.

"So clearly, patients lose response. Now, that lessens over time, but in the first year in psoriasis – and my guess is, in psoriatic arthritis as well – you have loss of effect at a relatively high level with all of these medicines," he said.

In fact, in the patient Dr. Gordon presented, a switch to adalimumab at a dose of 40 mg every other week resulted in an excellent initial response in both joints and skin, but skin symptoms returned after 8 months.

"This is something we’re all familiar with – patients doing well on an anti-TNF and then losing effect after a period of time on medication," he said.

So what are the alternatives?

An anti-TNF drug option after the patient cycles through etanercept, adalimumab, and infliximab is certolizumab, which was approved in September for the treatment of psoriatic arthritis. Study data suggest that the drug is "quite effective for psoriasis, was well tolerated, and similar to the other anti-TNFs," he said.

Using certolizumab is a reasonable approach that appears to work for both skin and joint symptoms, he said.

Golimumab is another possible option for treatment, but primary psoriasis data are lacking with this drug.

"It is my feeling that golimumab is probably not as potent for psoriasis as the other anti-TNF agents that we have, but that is an opinion," he said.

As for alternatives to anti-TNF agents, the PHEONIX 2 trial (Lancet 2008;371:1675-84) provided reasonable data in support of the interleukin-12 and -23 monoclonal antibody ustekinumab for skin disease, but patients who failed prior anti-TNF therapy actually had a poorer outcome, so that is something to keep in mind, he said, noting that adding methotrexate may help prevent a flare in patients who are switched from an anti-TNF agent to ustekinumab.

Ustekinumab, which also was approved in September for the treatment of psoriatic arthritis, is likely more useful for the skin, but is not exceptional for joint disease, he said at the meeting, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Apremilast and tofacitinib, drugs now in development for psoriasis, may also prove useful in the future, as they may "theoretically be of benefit" based on currently available data, he said.

Dr. Gordon has received research support and/or honoraria from AbbVie (which markets adalimumab), Amgen (which markets etanercept), Celgene (which is developing apremilast), Eli Lilly, Janssen (which markets golimumab, infliximab, and ustekinumab), Novartis, and Pfizer (which markets tofacitinib).