When switching from natalizumab to teriflunomide, timing is key

DALLAS – Teriflunomide could be a safe and effective option when patients with multiple sclerosis need to be switched from natalizumab, especially when the oral treatment starts 1 month after the last natalizumab treatment, according to a small, retrospective study.

Multiple studies have shown that natalizumab (Tysabri) is a risk factor for progressive multifocal leukoencephalopathy (PML). "So, there’s always the question of when do we switch," said Dr. Francisco J. Gomez, coauthor of the study and a physician at the MS Center of Northeastern New York in Latham.

"If you don’t switch people [from natalizumab] earlier in the disease, you might end up giving them worsened outcomes," Dr. Gomez said at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

At the same time, he noted, "you’re limited on how to switch. So you’re caught between a rock and a hard place. You want to switch them, but you don’t want to lose the only opportunity you have in controlling their disease."

Dr. Gomez and his colleagues looked at the safety and efficacy of teriflunomide (Aubagio), which was approved by theFood and Drug Administration in 2012 and has been shown to cut the annual MS relapse rate by more than a third.

The investigators used the center’s database to conduct a 12-month retrospective study of 30 patients who switched to teriflunomide after receiving natalizumab for more than a year and were all clinically stable. Most patients began the new treatment within 4 weeks of their last natalizumab treatment.

Cranial MRI and a clinical exam were conducted at the time of last natalizumab, and at 3 and 6 months after natalizumab treatment, to check for possible PML and new MS activity.

Of the 30 patients, 11 were triple positive for PML, meaning that they had received more than 24 natalizumab treatments, had prior immunosuppression, and were positive for anti–John Cunningham virus antibody. Fifteen were positive for anti-JCV antibody, and four were negative for anti-JCV antibody.

The mean number of natalizumab treatments was 38, ranging from 14 to 81. The patients’ mean age was 50 years, and 80% were female. Their mean duration of treatment with teriflunomide after natalizumab discontinuation was 13 months, ranging from 6 to 13.

Of all patients, 23 are still on teriflunomide, Dr. Gomez said. None have developed PML. Two have moved away and were lost to follow-up.

Five patients discontinued the treatment, one of whom developed significant exacerbation, including severe optic neuritis 4 weeks after starting on teriflunomide. That patient also had a 3-month delay between last natalizumab dose and the initiation of teriflunomide, compared with the rest, who started within a month of the last natalizumab treatment.

So, "a reduced washout period after natalizumab may be important to lessen breakthrough disease," Dr. Gomez and his colleagues said in the poster presented at the meeting.

Two others discontinued treatment because of persistent diarrhea and abdominal cramps, and one patient withdrew due to hair thinning. Minor diarrhea and transient hair thinning occurred in seven and five patients, respectively.

Despite the clinical exacerbations, "MRI scans haven’t shown disease, so we feel" that the disease is under control, Dr. Gomez said.

He advised physicians "to make the switch as soon as possible, no more than 4 weeks from the last natalizumab infusion, and then monitor the patient closely for potential MS relapse and PML for the next 6 months. Also, we have only been looking at patients switching to teriflunomide who have been stable while on natalizumab. If the patient has had exacerbations while on natalizumab, we usually go to rituximab and perhaps, in the future, alemtuzumab."

Dr. Gomez reported having no disclosures.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller

DALLAS – Teriflunomide could be a safe and effective option when patients with multiple sclerosis need to be switched from natalizumab, especially when the oral treatment starts 1 month after the last natalizumab treatment, according to a small, retrospective study.

Multiple studies have shown that natalizumab (Tysabri) is a risk factor for progressive multifocal leukoencephalopathy (PML). "So, there’s always the question of when do we switch," said Dr. Francisco J. Gomez, coauthor of the study and a physician at the MS Center of Northeastern New York in Latham.

"If you don’t switch people [from natalizumab] earlier in the disease, you might end up giving them worsened outcomes," Dr. Gomez said at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

At the same time, he noted, "you’re limited on how to switch. So you’re caught between a rock and a hard place. You want to switch them, but you don’t want to lose the only opportunity you have in controlling their disease."

Dr. Gomez and his colleagues looked at the safety and efficacy of teriflunomide (Aubagio), which was approved by theFood and Drug Administration in 2012 and has been shown to cut the annual MS relapse rate by more than a third.

The investigators used the center’s database to conduct a 12-month retrospective study of 30 patients who switched to teriflunomide after receiving natalizumab for more than a year and were all clinically stable. Most patients began the new treatment within 4 weeks of their last natalizumab treatment.

Cranial MRI and a clinical exam were conducted at the time of last natalizumab, and at 3 and 6 months after natalizumab treatment, to check for possible PML and new MS activity.

Of the 30 patients, 11 were triple positive for PML, meaning that they had received more than 24 natalizumab treatments, had prior immunosuppression, and were positive for anti–John Cunningham virus antibody. Fifteen were positive for anti-JCV antibody, and four were negative for anti-JCV antibody.

The mean number of natalizumab treatments was 38, ranging from 14 to 81. The patients’ mean age was 50 years, and 80% were female. Their mean duration of treatment with teriflunomide after natalizumab discontinuation was 13 months, ranging from 6 to 13.

Of all patients, 23 are still on teriflunomide, Dr. Gomez said. None have developed PML. Two have moved away and were lost to follow-up.

Five patients discontinued the treatment, one of whom developed significant exacerbation, including severe optic neuritis 4 weeks after starting on teriflunomide. That patient also had a 3-month delay between last natalizumab dose and the initiation of teriflunomide, compared with the rest, who started within a month of the last natalizumab treatment.

So, "a reduced washout period after natalizumab may be important to lessen breakthrough disease," Dr. Gomez and his colleagues said in the poster presented at the meeting.

Two others discontinued treatment because of persistent diarrhea and abdominal cramps, and one patient withdrew due to hair thinning. Minor diarrhea and transient hair thinning occurred in seven and five patients, respectively.

Despite the clinical exacerbations, "MRI scans haven’t shown disease, so we feel" that the disease is under control, Dr. Gomez said.

He advised physicians "to make the switch as soon as possible, no more than 4 weeks from the last natalizumab infusion, and then monitor the patient closely for potential MS relapse and PML for the next 6 months. Also, we have only been looking at patients switching to teriflunomide who have been stable while on natalizumab. If the patient has had exacerbations while on natalizumab, we usually go to rituximab and perhaps, in the future, alemtuzumab."

Dr. Gomez reported having no disclosures.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller

DALLAS – Teriflunomide could be a safe and effective option when patients with multiple sclerosis need to be switched from natalizumab, especially when the oral treatment starts 1 month after the last natalizumab treatment, according to a small, retrospective study.

Multiple studies have shown that natalizumab (Tysabri) is a risk factor for progressive multifocal leukoencephalopathy (PML). "So, there’s always the question of when do we switch," said Dr. Francisco J. Gomez, coauthor of the study and a physician at the MS Center of Northeastern New York in Latham.

"If you don’t switch people [from natalizumab] earlier in the disease, you might end up giving them worsened outcomes," Dr. Gomez said at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

At the same time, he noted, "you’re limited on how to switch. So you’re caught between a rock and a hard place. You want to switch them, but you don’t want to lose the only opportunity you have in controlling their disease."

Dr. Gomez and his colleagues looked at the safety and efficacy of teriflunomide (Aubagio), which was approved by theFood and Drug Administration in 2012 and has been shown to cut the annual MS relapse rate by more than a third.

The investigators used the center’s database to conduct a 12-month retrospective study of 30 patients who switched to teriflunomide after receiving natalizumab for more than a year and were all clinically stable. Most patients began the new treatment within 4 weeks of their last natalizumab treatment.

Cranial MRI and a clinical exam were conducted at the time of last natalizumab, and at 3 and 6 months after natalizumab treatment, to check for possible PML and new MS activity.

Of the 30 patients, 11 were triple positive for PML, meaning that they had received more than 24 natalizumab treatments, had prior immunosuppression, and were positive for anti–John Cunningham virus antibody. Fifteen were positive for anti-JCV antibody, and four were negative for anti-JCV antibody.

The mean number of natalizumab treatments was 38, ranging from 14 to 81. The patients’ mean age was 50 years, and 80% were female. Their mean duration of treatment with teriflunomide after natalizumab discontinuation was 13 months, ranging from 6 to 13.

Of all patients, 23 are still on teriflunomide, Dr. Gomez said. None have developed PML. Two have moved away and were lost to follow-up.

Five patients discontinued the treatment, one of whom developed significant exacerbation, including severe optic neuritis 4 weeks after starting on teriflunomide. That patient also had a 3-month delay between last natalizumab dose and the initiation of teriflunomide, compared with the rest, who started within a month of the last natalizumab treatment.

So, "a reduced washout period after natalizumab may be important to lessen breakthrough disease," Dr. Gomez and his colleagues said in the poster presented at the meeting.

Two others discontinued treatment because of persistent diarrhea and abdominal cramps, and one patient withdrew due to hair thinning. Minor diarrhea and transient hair thinning occurred in seven and five patients, respectively.

Despite the clinical exacerbations, "MRI scans haven’t shown disease, so we feel" that the disease is under control, Dr. Gomez said.

He advised physicians "to make the switch as soon as possible, no more than 4 weeks from the last natalizumab infusion, and then monitor the patient closely for potential MS relapse and PML for the next 6 months. Also, we have only been looking at patients switching to teriflunomide who have been stable while on natalizumab. If the patient has had exacerbations while on natalizumab, we usually go to rituximab and perhaps, in the future, alemtuzumab."

Dr. Gomez reported having no disclosures.

nmiller@frontlinemedcom.com

On Twitter @naseemmiller