KEVZARA combination therapy demonstrated rapid, sustained, consistent clinical response^1-3

[Introduction. 00:00-00:11]

Hello, my name is Audrey Gibson and I’m a physician assistant at the Arthritis Center of North Georgia.

I’m excited to share some information with you about KEVZARA in combination therapy.

[KEVZARA Indication and Boxed Warning. 00:11-00:44]

KEVZARA is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis, who have an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. Patients treated with KEVZARA are at an increased risk for developing serious infections that may lead to hospitalization or death. Avoid use of KEVZARA in patients with an active infection and closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. This will be discussed more, along with additional important safety information, later in this video.¹

[Factors that influence decision to prescribe concomitant therapy. 00:44-01:14]
“When considering a concomitant therapy, what factors influence your decision on what to prescribe?”
When considering a concomitant therapy for my RA patients, first I look closely at the clinical trial data. For KEVZARA, the trials that are most important to me in this context are MOBILITY, which evaluated the methotrexate inadequate responder population; TARGET, which evaluated TNF inadequate responder patients; and EXTEND, which is a long-term extension study of KEVZARA in combination with methotrexate or other DMARDs.^1,4

[MOBILITY trial study design. 01:14-01:46]
First let’s look at MOBILITY. MOBILITY was a 52-week, randomized, double-blind, placebo-controlled, multi-center study, which included 1,197 patients. It assessed the efficacy and safety of KEVZARA 200 milligrams plus methotrexate, and 150 milligrams plus methotrexate, in patients with moderate to severe active rheumatoid arthritis, with a duration of at least three months, who had been on methotrexate 10 milligrams to 25 milligrams per week for at least six weeks.^1,2

[TARGET trial study design. 01:46-02:20]
Next, let’s look at TARGET. TARGET was a 24-week randomized, double-blind parallel group, placebo-controlled, multi-center study, which included 546 patients. It assessed the efficacy and safety of KEVZARA 200 milligrams, and 150 milligrams added to background conventional DMARDs in patients with moderate to severe active rheumatoid arthritis, with a duration of at least six months, with inadequate response and/or intolerance to one or more TNF antagonists, when administered with background conventional DMARDs.^1,3

[MOBILITY and TARGET patients enrolled. 02:20-02:45]
The patient population of both MOBILITY and TARGET are relevant as it is representative of the types of patients that I see in my practice. These are patients that have failed both methotrexate and one or more TNFs.
When I look at the data, it is notable that, in all three study arms for TARGET, over 20 percent of patients had cycled through multiple TNFs. And so that gives me confidence that these trials are characteristic of what I see in my patients in real life.³

[MOBILITY and TARGET coprimary endpoints. 02:45-03:05]
Let’s take a look at the co-primary endpoints. The co-primary endpoints evaluated were the proportion of patients who achieved an ACR20 response at Week 24, the change from baseline in HAQ-DI at Week 16 in MOBILITY and Week 12 in TARGET, and the change from baseline in mean total Sharp score at Week 52 in MOBILITY.¹

[MOBILITY and TARGET efficacy data. 03:05-04:40]
Now let’s take a look at the outcomes. As you can see, there were consistent results across both trials.
Looking at MOBILITY, significantly more patients in the KEVZARA 200 milligram plus methotrexate group achieved an ACR20 response at 24 weeks, compared to placebo plus methotrexate group: 66 percent versus 33 percent, respectively.^1,2
Now, let’s look at TARGET. Significantly more patients in the KEVZARA 200 milligram plus DMARD group achieved an ACR20 response at 24 weeks than in the placebo plus DMARD group: 61 percent versus 34 percent, respectively. Now, keep in mind that these are patients that have failed one or more TNFs.^1,3
I’m excited about the consistency across trials, because I find replication of results is the hallmark of scientific rigor. And it helps me feel that I am making more informed decisions when prescribing.
Other information that I found interesting was that the third co-primary endpoint in the MOBILITY trial, was change from baseline in mean total Sharp scores at 52 weeks. Both doses of KEVZARA plus methotrexate were associated with significantly less radiographic progression of structural damage compared with placebo plus methotrexate at 52 weeks. Improvements were also observed with both doses of KEVZARA at 24 weeks.^1,2
More than half of patients—55.6 percent—receiving KEVZARA 200 milligrams plus methotrexate, had no evidence of any radiographic progression at 52 weeks, compared with 38.7 percent of patients receiving placebo plus methotrexate.²

[MOBILITY and TARGET safety data. 04:40-05:03]
Next, let’s look at some of the safety data. In here, you can see the most common adverse reactions in the trials: neutropenia, increased ALT, and injection site erythema. For the most frequent adverse events, KEVZARA demonstrated 10 percent, five percent, and four percent versus 0.2 percent, two percent, and 0.9 percent with placebo.¹

[Consider KEVZARA for your patients with RA. 05:03-05:54]
When talking to a patient, and I can tell that they’re not doing well, this is when I discuss making a change in their medication.
I consider combination therapy in any patient who is not doing well on their current drug regimen—any patient that is having persistent joint pain, or swelling, or having more flares.
I suggest that it may be time for a change.
I have chosen KEVZARA as a treatment when patients have failed both methotrexate and TNFs. I have made this decision based off data from both the MOBILITY and the TARGET trials.¹
There is more information available that can help you better understand the long-term efficacy and safety of KEVZARA. Although not a focus of this video, I encourage you to look at the Open Label Extension trial EXTEND, which followed patients out to seven years. This data is available on combination therapy page on this website.

INDICATION

KEVZARA® (sarilumab) is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION
Do not use KEVZARA in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.

WARNINGS AND PRECAUTIONS

• Infections. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including KEVZARA. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA. The most frequently observed serious infections with KEVZARA in RA patients included pneumonia and cellulitis.
  • Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
  • Patients with latent TB should be treated with standard antimycobacterial therapy before initiating KEVZARA. Consider anti-TB therapy prior to initiation of KEVZARA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection.
  • Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have: chronic or recurrent infection, a history of serious or opportunistic infections, underlying conditions that may predispose them to infection, been exposed to TB, or lived in or traveled to areas of endemic TB or endemic mycoses.
  • Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with KEVZARA.
• Laboratory Abnormalities. Treatment with KEVZARA was associated with decreases in absolute neutrophil counts (including neutropenia), and platelet counts; and increases in transaminase levels and lipid parameters (LDL, HDL cholesterol, and/or triglycerides). Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with KEVZARA. Assess neutrophil count, platelet count, and ALT/AST levels prior to initiation with KEVZARA. Monitor these parameters 4 to 8 weeks after start of therapy and every 3 months thereafter. Assess lipid parameters 4 to 8 weeks after start of therapy, then at 6 month intervals.
• Gastrointestinal Perforation. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Gastrointestinal perforations have been reported in clinical studies, primarily as complications of diverticulitis. Promptly evaluate patients presenting with new onset abdominal symptoms.
• Immunosuppression. Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with KEVZARA on the development of malignancies is not known but malignancies have been reported in clinical studies.
• Hypersensitivity Reactions. Hypersensitivity reactions have been reported in association with KEVZARA. Hypersensitivity reactions that required treatment discontinuation were reported in 0.3% of patients in controlled RA trials. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of KEVZARA immediately. Do not administer KEVZARA to patients with known hypersensitivity to sarilumab. 
• Active Hepatic Disease and Hepatic Impairment. Treatment with KEVZARA is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with KEVZARA was associated with transaminase elevations.
• Live Vaccines. Avoid concurrent use of live vaccines during treatment with KEVZARA due to potentially increased risk of infections. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving KEVZARA. Prior to initiating treatment, it is recommended that all patients be brought up to date with all immunizations in agreement with current immunization guidelines.

ADVERSE REACTIONS

• For Rheumatoid Arthritis: The most common serious adverse reactions were infections. The most frequently observed serious infections included pneumonia and cellulitis. The most common adverse reactions (occurred in at least 3% of patients treated with KEVZARA + DMARDs) are neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.

DRUG INTERACTIONS

• Exercise caution when KEVZARA is co-administered with CYP substrates with a narrow therapeutic index (e.g. warfarin or theophylline), or with CYP3A4 substrates (e.g. oral contraceptives or statins) as there may be a reduction in exposure which may reduce the activity of the CYP3A4 substrate.
• Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.

USE IN SPECIFIC POPULATIONS

• KEVZARA should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because monoclonal antibodies could be excreted in small amounts in human milk, the benefits of breastfeeding and the potential adverse effects on the breastfed child should be considered along with the mother’s clinical need for KEVZARA.
• Use caution when treating the elderly.

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Please click here to see full Prescribing Information, including Boxed WARNING.