Article Type
Changed
Mon, 06/28/2021 - 13:55
Display Headline
Dr. Jayatilleke: Treatment options are limited for RA patients who have ILD or other pulmonary complications.
Dr. Jayatilleke scans the journals, so you don't have to!

Arundathi Jayatilleke, MD
Several recent RA studies looked at safety and efficacy of novel therapies for RA. Takeuchi et al present safety and efficacy data from a long-term open-label extension trial of peficitinib, a pan-JAK inhibitor, in Asian patients with RA. Peficitinib was generally well-tolerated, with sustained ACR20/50/70 response rates from the beginning of the open-label extension. Notably, with respect to safety, treatment-emergent adverse effects included nasopharyngitis and herpes zoster, a known risk from prior studies of tofacitinib. On the other hand, venous thromboembolism was rare. While this open-label extension study does not include a placebo comparator, it does provide support for longer-term efficacy of peficitinib in Asian patients, with comparable rates of adverse events to other JAK inhibitors.

 


Iguratimod (IGU) is a novel small-molecule synthetic DMARD being studied for RA; its exact mechanism is unknown, but it inhibits NF-kB activation and seems to reduce bone resorption via RANKL and cartilage erosion via matrix metalloproteinases. Currently, it is approved in Japan and China for treatment of RA; initial studies from 2008-2010 showed improved ACR20 rates compared to placebo and comparable rates with methotrexate monotherapy; combination therapy with methotrexate appears to be more effective than either methotrexate or IGU monotherapy. Yoshikawa et al present a small study of 47 patients receiving methotrexate or methotrexate with IGU and show promising results regarding tapering of methotrexate with sustained remission/low disease activity and decrease in ultrasound evidence of synovitis in patients receiving IGU, suggesting that it is a reasonable longer-term option for RA patients. However, the medication is not approved in the US, nor have studies in patients in the US been published, so generalizability in patients outside of Japan and China is uncertain, in addition to concerns related to the small sample size.

 

In contrast, tocilizumab is an established therapy for RA; Pappas et al present real-world clinical practice data from the Corrona RA registry. Among nearly 1800 RA patients who initiated tocilizumab therapy, the mean durability of response was over 3 years in terms of maintaining minimum clinically important difference (MCID) over baseline CDAI and over 1 year in terms of maintaining low disease activity. Most patients in the study had previously received biologic therapy. Though the observational nature of the study limits its generalizability, the addition of efficacy data to persistence on therapy lend weight to this evidence regarding durability of response to tocilizumab, as the proportion of patients maintaining MCID was >50% at 3 years.

 

Treatment options are limited for RA patients who have ILD or other pulmonary complications. The fear of causing or exacerbating pulmonary toxicity limits the use of methotrexate, leflunomide, and anti-TNF biologics. Some data support the safety of rituximab and abatacept. A retrospective observational study looked at outcomes in RA patients on rituximab and JAK inhibitors. Reassuringly, respiratory event rates were no different between the two groups though number of patients and trial design prevents wider generalization; it is also unknown whether RA-ILD improves with ritixumab or JAK-inhibition. However, given these results, studying JAK inhibitors in larger prospective studies would be reasonable.

 

Author and Disclosure Information

Arundathi Jayatilleke, MD
Lewis Katz School of Medicine, Temple University

Publications
Topics
Sections
Author and Disclosure Information

Arundathi Jayatilleke, MD
Lewis Katz School of Medicine, Temple University

Author and Disclosure Information

Arundathi Jayatilleke, MD
Lewis Katz School of Medicine, Temple University

Dr. Jayatilleke scans the journals, so you don't have to!
Dr. Jayatilleke scans the journals, so you don't have to!

Arundathi Jayatilleke, MD
Several recent RA studies looked at safety and efficacy of novel therapies for RA. Takeuchi et al present safety and efficacy data from a long-term open-label extension trial of peficitinib, a pan-JAK inhibitor, in Asian patients with RA. Peficitinib was generally well-tolerated, with sustained ACR20/50/70 response rates from the beginning of the open-label extension. Notably, with respect to safety, treatment-emergent adverse effects included nasopharyngitis and herpes zoster, a known risk from prior studies of tofacitinib. On the other hand, venous thromboembolism was rare. While this open-label extension study does not include a placebo comparator, it does provide support for longer-term efficacy of peficitinib in Asian patients, with comparable rates of adverse events to other JAK inhibitors.

 


Iguratimod (IGU) is a novel small-molecule synthetic DMARD being studied for RA; its exact mechanism is unknown, but it inhibits NF-kB activation and seems to reduce bone resorption via RANKL and cartilage erosion via matrix metalloproteinases. Currently, it is approved in Japan and China for treatment of RA; initial studies from 2008-2010 showed improved ACR20 rates compared to placebo and comparable rates with methotrexate monotherapy; combination therapy with methotrexate appears to be more effective than either methotrexate or IGU monotherapy. Yoshikawa et al present a small study of 47 patients receiving methotrexate or methotrexate with IGU and show promising results regarding tapering of methotrexate with sustained remission/low disease activity and decrease in ultrasound evidence of synovitis in patients receiving IGU, suggesting that it is a reasonable longer-term option for RA patients. However, the medication is not approved in the US, nor have studies in patients in the US been published, so generalizability in patients outside of Japan and China is uncertain, in addition to concerns related to the small sample size.

 

In contrast, tocilizumab is an established therapy for RA; Pappas et al present real-world clinical practice data from the Corrona RA registry. Among nearly 1800 RA patients who initiated tocilizumab therapy, the mean durability of response was over 3 years in terms of maintaining minimum clinically important difference (MCID) over baseline CDAI and over 1 year in terms of maintaining low disease activity. Most patients in the study had previously received biologic therapy. Though the observational nature of the study limits its generalizability, the addition of efficacy data to persistence on therapy lend weight to this evidence regarding durability of response to tocilizumab, as the proportion of patients maintaining MCID was >50% at 3 years.

 

Treatment options are limited for RA patients who have ILD or other pulmonary complications. The fear of causing or exacerbating pulmonary toxicity limits the use of methotrexate, leflunomide, and anti-TNF biologics. Some data support the safety of rituximab and abatacept. A retrospective observational study looked at outcomes in RA patients on rituximab and JAK inhibitors. Reassuringly, respiratory event rates were no different between the two groups though number of patients and trial design prevents wider generalization; it is also unknown whether RA-ILD improves with ritixumab or JAK-inhibition. However, given these results, studying JAK inhibitors in larger prospective studies would be reasonable.

 

Arundathi Jayatilleke, MD
Several recent RA studies looked at safety and efficacy of novel therapies for RA. Takeuchi et al present safety and efficacy data from a long-term open-label extension trial of peficitinib, a pan-JAK inhibitor, in Asian patients with RA. Peficitinib was generally well-tolerated, with sustained ACR20/50/70 response rates from the beginning of the open-label extension. Notably, with respect to safety, treatment-emergent adverse effects included nasopharyngitis and herpes zoster, a known risk from prior studies of tofacitinib. On the other hand, venous thromboembolism was rare. While this open-label extension study does not include a placebo comparator, it does provide support for longer-term efficacy of peficitinib in Asian patients, with comparable rates of adverse events to other JAK inhibitors.

 


Iguratimod (IGU) is a novel small-molecule synthetic DMARD being studied for RA; its exact mechanism is unknown, but it inhibits NF-kB activation and seems to reduce bone resorption via RANKL and cartilage erosion via matrix metalloproteinases. Currently, it is approved in Japan and China for treatment of RA; initial studies from 2008-2010 showed improved ACR20 rates compared to placebo and comparable rates with methotrexate monotherapy; combination therapy with methotrexate appears to be more effective than either methotrexate or IGU monotherapy. Yoshikawa et al present a small study of 47 patients receiving methotrexate or methotrexate with IGU and show promising results regarding tapering of methotrexate with sustained remission/low disease activity and decrease in ultrasound evidence of synovitis in patients receiving IGU, suggesting that it is a reasonable longer-term option for RA patients. However, the medication is not approved in the US, nor have studies in patients in the US been published, so generalizability in patients outside of Japan and China is uncertain, in addition to concerns related to the small sample size.

 

In contrast, tocilizumab is an established therapy for RA; Pappas et al present real-world clinical practice data from the Corrona RA registry. Among nearly 1800 RA patients who initiated tocilizumab therapy, the mean durability of response was over 3 years in terms of maintaining minimum clinically important difference (MCID) over baseline CDAI and over 1 year in terms of maintaining low disease activity. Most patients in the study had previously received biologic therapy. Though the observational nature of the study limits its generalizability, the addition of efficacy data to persistence on therapy lend weight to this evidence regarding durability of response to tocilizumab, as the proportion of patients maintaining MCID was >50% at 3 years.

 

Treatment options are limited for RA patients who have ILD or other pulmonary complications. The fear of causing or exacerbating pulmonary toxicity limits the use of methotrexate, leflunomide, and anti-TNF biologics. Some data support the safety of rituximab and abatacept. A retrospective observational study looked at outcomes in RA patients on rituximab and JAK inhibitors. Reassuringly, respiratory event rates were no different between the two groups though number of patients and trial design prevents wider generalization; it is also unknown whether RA-ILD improves with ritixumab or JAK-inhibition. However, given these results, studying JAK inhibitors in larger prospective studies would be reasonable.

 

Publications
Publications
Topics
Article Type
Display Headline
Dr. Jayatilleke: Treatment options are limited for RA patients who have ILD or other pulmonary complications.
Display Headline
Dr. Jayatilleke: Treatment options are limited for RA patients who have ILD or other pulmonary complications.
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Article Series
Clinical Edge Journal Scan: RA April 2021
Gate On Date
Tue, 04/06/2021 - 10:45
Un-Gate On Date
Tue, 04/06/2021 - 10:45
Use ProPublica
CFC Schedule Remove Status
Tue, 04/06/2021 - 10:45
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article