In the JournalsPerspective

Filgotinib improves RA signs, symptoms in DMARD-refractory patients

Mark C. Genovese

Patients with rheumatoid arthritis who previously had an inadequate response to biologic DMARDs demonstrated improved signs and symptoms after receiving daily doses of filgotinib, according to data published in JAMA.

“The study demonstrates that this new selective JAK1 inhibitor works well in patients who have failed standard of care therapies,” Mark C. Genovese, MD, of the Stanford University School of Medicine, told Healio Rheumatology. “The greatest significance to me was the number of patients who could achieve low disease or even remission at 12 and at 24 weeks in this refractory group, including those who had failed three or more biologic agents.”

To analyze the impact filgotinib (Galapagos NV) has – compared with placebo – on the signs and symptoms of RA among patients who experienced little or no relief from biologic DMARDs, Genovese and colleagues conducted the phase 3 FINCH 2 study, a 24-week, randomized trial of 449 adults in 114 centers, across 15 countries in North America and Europe. All participants were aged 18 years or older, with moderate-to-severe active RA and a previous inadequate response or an intolerance to one or more biological DMARD.

 
Patients with RA who previously had an inadequate response to biologic DMARDs demonstrated improved signs and symptoms after receiving filgotinib, according to data.
Source: Adobe

Participants were randomly assigned to receive either 100 mg or 200 mg of filgotinib, or placebo, once daily. Patients also continued stable treatment with conventional synthetic DMARDs. The primary outcome was the proportion of participants achieving ACR20 criteria at week 12. Secondary endpoints included low disease activity, change in health assessment questionnaire-disability index, 36-item short-form health survey physical component and functional assessment of chronic illness therapy-fatigue scores at week 12. Genovese and colleagues also assessed 12-week remission and adverse events.

According to the researchers, 381 participants completed the study. At week 12, 66% of patients treated with 200 mg of filgotinib, as well as 57.5% of those in the 100-mg group, demonstrated ACR20 response, compared with 31.1% of those who received placebo (P < .001). This included patients with prior, inadequate treatments with three or more biologic DMARDs — 70.3% in the 200-mg group, 58.8% in the 100-mg group and 17.6% among those who received placebo (P < .001).

The most common adverse events included nasopharyngitis, reported in 10.2% of patients in the 200-mg group, as well as headache, nasopharyngitis and upper respiratory infection, with each experienced by 5.9% of patients in the 100-mg group. In addition, there were four uncomplicated cases of herpes zoster and one retinal vein occlusion among patients treated with filgotinib. There were no opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations or deaths.

“This is continuing to evolve based on the results of the phase 3 program and the integrated safety across all studies done to date,” Genovese said. “I’m hoping that regulators and insurers can make this data available for as broad a population as possible. This report should provide optimism and hope for those patients who are getting inadequate responses from their current therapy.”

In a related editorial, Jasvinder A. Singh, MBBS, MPH, of the University of Alabama at Birmingham, called the study and the resulting data “pivotal” for patients with RA who are nonresponsive or intolerant to current treatments. However, he added that the price of oral JAK inhibitors will have to be reduced to help promote their use.

“Patients and clinicians express frustration over the high pricing of new RA therapies because a portion of the cost is often passed on to the patients by the health insurance plan, which limits access to these therapies,” Singh wrote in JAMA. “Head-to-head comparison of filgotinib with other JAK inhibitors, biologic DMARDs, and triple conventional DMARD therapy will further define the most appropriate use of filgotinib for patients with RA by examining the comparative efficacy and safety.” – by Jason Laday

Disclosure : Genovese reports grants and personal fees from AbbVie, Astellas, Eli Lilly, EMD Serono, Genentech/Roche, Gilead, Pfizer, Sanofi and Vertex, as well as grants from Galapagos. Please see the full study for additional authors’ disclosures. Singh reports personal fees from the ACR, ClearView Healthcare Partners, Clinical Care Options, Fidia, Horizon, Medisys, Medscape, the NIH, Putnam Associates, Spherix, UBM LLC and WebMD; owning stock options in Amarin Pharmaceuticals and Viking Therapeutics; and serving on the OMERACT executive board, the FDA advisory committee and the Veterans Affairs Rheumatology Field Advisory Committee.

Mark C. Genovese

Patients with rheumatoid arthritis who previously had an inadequate response to biologic DMARDs demonstrated improved signs and symptoms after receiving daily doses of filgotinib, according to data published in JAMA.

“The study demonstrates that this new selective JAK1 inhibitor works well in patients who have failed standard of care therapies,” Mark C. Genovese, MD, of the Stanford University School of Medicine, told Healio Rheumatology. “The greatest significance to me was the number of patients who could achieve low disease or even remission at 12 and at 24 weeks in this refractory group, including those who had failed three or more biologic agents.”

To analyze the impact filgotinib (Galapagos NV) has – compared with placebo – on the signs and symptoms of RA among patients who experienced little or no relief from biologic DMARDs, Genovese and colleagues conducted the phase 3 FINCH 2 study, a 24-week, randomized trial of 449 adults in 114 centers, across 15 countries in North America and Europe. All participants were aged 18 years or older, with moderate-to-severe active RA and a previous inadequate response or an intolerance to one or more biological DMARD.

 
Patients with RA who previously had an inadequate response to biologic DMARDs demonstrated improved signs and symptoms after receiving filgotinib, according to data.
Source: Adobe

Participants were randomly assigned to receive either 100 mg or 200 mg of filgotinib, or placebo, once daily. Patients also continued stable treatment with conventional synthetic DMARDs. The primary outcome was the proportion of participants achieving ACR20 criteria at week 12. Secondary endpoints included low disease activity, change in health assessment questionnaire-disability index, 36-item short-form health survey physical component and functional assessment of chronic illness therapy-fatigue scores at week 12. Genovese and colleagues also assessed 12-week remission and adverse events.

According to the researchers, 381 participants completed the study. At week 12, 66% of patients treated with 200 mg of filgotinib, as well as 57.5% of those in the 100-mg group, demonstrated ACR20 response, compared with 31.1% of those who received placebo (P < .001). This included patients with prior, inadequate treatments with three or more biologic DMARDs — 70.3% in the 200-mg group, 58.8% in the 100-mg group and 17.6% among those who received placebo (P < .001).

The most common adverse events included nasopharyngitis, reported in 10.2% of patients in the 200-mg group, as well as headache, nasopharyngitis and upper respiratory infection, with each experienced by 5.9% of patients in the 100-mg group. In addition, there were four uncomplicated cases of herpes zoster and one retinal vein occlusion among patients treated with filgotinib. There were no opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations or deaths.

“This is continuing to evolve based on the results of the phase 3 program and the integrated safety across all studies done to date,” Genovese said. “I’m hoping that regulators and insurers can make this data available for as broad a population as possible. This report should provide optimism and hope for those patients who are getting inadequate responses from their current therapy.”

In a related editorial, Jasvinder A. Singh, MBBS, MPH, of the University of Alabama at Birmingham, called the study and the resulting data “pivotal” for patients with RA who are nonresponsive or intolerant to current treatments. However, he added that the price of oral JAK inhibitors will have to be reduced to help promote their use.

“Patients and clinicians express frustration over the high pricing of new RA therapies because a portion of the cost is often passed on to the patients by the health insurance plan, which limits access to these therapies,” Singh wrote in JAMA. “Head-to-head comparison of filgotinib with other JAK inhibitors, biologic DMARDs, and triple conventional DMARD therapy will further define the most appropriate use of filgotinib for patients with RA by examining the comparative efficacy and safety.” – by Jason Laday

Disclosure : Genovese reports grants and personal fees from AbbVie, Astellas, Eli Lilly, EMD Serono, Genentech/Roche, Gilead, Pfizer, Sanofi and Vertex, as well as grants from Galapagos. Please see the full study for additional authors’ disclosures. Singh reports personal fees from the ACR, ClearView Healthcare Partners, Clinical Care Options, Fidia, Horizon, Medisys, Medscape, the NIH, Putnam Associates, Spherix, UBM LLC and WebMD; owning stock options in Amarin Pharmaceuticals and Viking Therapeutics; and serving on the OMERACT executive board, the FDA advisory committee and the Veterans Affairs Rheumatology Field Advisory Committee.

    Perspective
    David A. McLain

    David A. McLain

    JAK inhibitors have been approved by the FDA and are being used for rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Ruxolitinib (Jakafi, Incyte) is FDA approved for myelofibrosis, polycythemia vera and acute graft-versus-host disease. JAK inhibitors are also being studied for Crohn’s disease, lupus, psoriasis, alopecia areata and totalis, hematologic malignancies, acute myelocytic leukemia, essential thrombocythemia, myelodysplastic syndrome, metastatic pancreatic carcinoma and vitiligo (topically) among other indications.

    Only two JAK inhibitors have been approved for use in rheumatologic conditions in the United States: Tofacitinib (Xeljanz, Pfizer) relatively selective for JAK1 and JAK3 and FDA-approved for RA and PsA, and; baricitinib (Olumiant, Eli Lilly) relatively selective for JAK1 and JAK2 and FDA-approved for RA. However, two newer agents are currently under development for rheumatologic conditions: Upadacitinib (AbbVie) and filgotinib (Galapagos NV), which are both selective for JAK1.

    In the current study, the researchers conducted a 24-week double-blind, placebo-controlled, international multicenter trial of filgotinib for RA, with no comparison made to other already approved biologic DMARDs (bDMARDs) or other JAK inhibitors.

    Patients who had failed a JAK inhibitor were not permitted in the study but other treatment failures were permitted, including bDMARDs and including rituximab (Rituxan, Genentech). In fact, 75% of the patients had been on a bDMARD with 25% on three or more bDMARDs. Approximately, 70% of patients were on prednisone with the average dose of 6.5 mg per day, and 90% had been on a conventional DMARD with methotrexate representing the vast majority with an average dose of 16 mg per week.

    The mean age of the participants was 56 years with over 25% being over 65 years old. The duration of rheumatoid arthritis averaged 10 years. This group is representative of the patients we see in clinic who have “been around” and thus the results are impressive.

    • David A. McLain, MD, FACP, FACR
    • Executive director, Alabama Society for the Rheumatic Diseases
      Symposium director, Congress of Clinical Rheumatology

    Disclosures: McLain reports no relevant financial disclosures.