Biologics For Rheumatoid Arthritis In People Not Previously Treated With Methotrexate
We studied the benefits and harms of biologics or tofacitinib on people with rheumatoid arthritis who have not previously been treated with methotrexate , in trials done until June 2015. Data was available for four TNF biologics and two non-TNF biologics .
What is RA and what are biologics/tofacitinib?
In RA, the immune system, which normally fights infection, attacks the joint lining making it inflamed. Without treatment, the inflammation can lead to joint damage and disability. Biologics or tofacitinib are medications that can reduce joint inflammation/damage and improve symptoms.
The review shows that in people with RA:
– Biologics in combination with MTX probably improve signs and symptoms of RA , the chances of RA remission and probably slightly improve functional ability. We downgraded our confidence in the results because of concerns about the inconsistency of some results.
– Biologics in combination with MTX may make little or no difference in the risk of serious adverse events or withdrawals due to adverse events. We downgraded our confidence in the results because of concerns about the inconsistency of some results and the lack of data.
– We often do not have precise information about side effects and complications. Because of the lack of data, we are uncertain of the effect of biologics on the risk of cancer.
-TNF biologics alone probably make little or no difference in signs and symptoms of RA or chances of RA remission .
What Is The First Line Of Drug Treatment For Ra
Your rheumatoid arthritis drug treatment will be uniquely tailored to your needs. Your doctor will discuss the risks and benefits of drug treatment with you. Treatment will depend upon the severity and length of time you have had RA.
Your doctor may start treatment by prescribing one or more disease-modifying anti-rheumatic drugs .
A drug from the nonsteroidal or glucocorticoid anti-inflammatory drug class might be used initially or for more severe RA symptoms to control your acute pain and inflammation.
Costs Of Biologics In Ra
In a retrospective study of US health plan costs related to RA, etanercept was associated with lower drug and outpatient costs than infliximab and adalimumab. Infliximab and adalimuab had RA-related monthly total healthcare costs that were 1.55 times and 1.12 times greater, respectively, than corresponding costs for etanercept. The study also observed a greater difference between start- and end-dispensing doses of infliximab than adalimumab and etanercept .
In an economic evaluation of TNF-antagonist use in the UK, incremental cost-effectiveness ratios were Â£30,000 per QALY in early RA versus Â£50,000 per QALY in late RA. TNF antagonists were most cost-effective when used as the third-line agent in a sequence of DMARDs: ICERs were Â£24,000 per QALY for etanercept Â£30,000 per QALY for adalimumab and Â£38,000 per QALY for infliximab. Importantly, the cost-effectiveness of these agents is likely to be comparatively better than in the United States, where biologic use in patients with mild to moderate disease is more common in clinical practice.
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Do You Prefer A Shot Or Iv
Biologics can be given as an injection or intravenously . You and your doctor will want to consider what is best and most convenient for you when choosing a biologic.
You give yourself a shot at home — convenient, but some people are uneasy about giving themselves a shot.
You may be able to go to your doctorâs office to get the shots.
Must be given at a hospital or clinic.
Risk of injection site reactions such as rash, burning, or itching.
Kineret had the highest rate of injection site reactions, according to an analysis by Consumer Reports in 2010.
Risk of infusion reactions including itching, hives, rash, nausea, and headache.
Rituxan had the highest rate of infusion reactions and Orencia the lowest, according to the 2010 Consumer Reports analysis.
Shots are needed more frequently than infusions.
Frequency ranges from daily shots to a shot every month.
Infusions can take several hours but are usually only needed every month or two.
Infusions may be needed more often during the first year of treatment, which can increase initial costs.
Focus On Remission: Early Aggressive Treatment And Optimal Switching Patterns
Treatment of RA should be aimed at achieving the lowest possible disease activity and, ideally, disease remission. Although clinicians have typically reserved biologics for patients with severe disease who have failed other therapies, there is now a shift towards biologic use in selected patients with early RA and high disease activity. Clinical and radiographic data consistently show that early, aggressive treatment can improve the potential for superior clinical responses and remission compared with later treatment of established RA. These data suggest the existence of a âwindow of opportunityâ, during which the natural disease course may be altered. However, formulary restrictions often require RA patients to wait â¥6 months after starting DMARD therapy before allowing the use of biologic agents, which for some patients may result in irreversible joint damage. Importantly, improving outcomes with early treatment strategies may reduce healthcare costs and morbidity in the long term, thereby offsetting the relatively high direct treatment costs associated with biologics.
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Do Biologics Have Side Effects
The most common are pain and rash where you got the shot. But they affect only a small number of people who take these drugs. Biologics can cause allergic reactions. Because some go directly into a vein, youâll get the infusion at a place where your doctor can keep an eye on you. Reaction symptoms include flu-like illness, fever, chills, nausea, and headache.
As with any drugs that suppress your immune system, biologics can make you more likely to get infections and other diseases. See the doctor ASAP if you have a fever or unexplained symptoms. You may need to get vaccinations to prevent infections before you start a biologic. Talk to your doctor before getting a vaccination if you’re on a biologic.
Other Immunomodulatory And Cytotoxic Agents
Some additional immunomodulatory drugs are used in RA including azathioprine , and cyclosporin A . Rarely cyclophosphamide and d-Penicillamine are used. Because the potential of high toxicity, these agents are typically utilized for life-threatening extra-articular manifestations of RA such as systemic vasculitis or with severe articular disease that is refractory to other therapy.
Azathioprine has some activity in rheumatoid arthritis but may take 8-12 weeks to see an effect. It is a purine analog that can cause bone marrow suppression and lowering of blood cell counts particularly in patients with renal insufficiency or when used concomitantly with allopurinol or ACE inhibitors. Increased risk of secondary malignancy due to azathioprine is controversial. Screening for levels of the enzyme thiopurine methyltransferase is recommended before initiating therapy with azathioprine. Certain individuals have deficiencies in this enzyme that metabolizes azathioprine with a concomitantly increased risk of toxicitiy for the medication. Side effects include nausea, and alopecia. Blood tests to monitor blood counts and liver function tests are necessary for patients on azathioprine.
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Who Shouldnt Take Them
Biologics may cause some dormant chronic diseases to flare. They may not be a good idea if you have multiple sclerosis or other conditions like severe congestive heart failure. Your doctor will give you a skin or blood test for tuberculosis before you start a biologic. You also need a test for chronic hepatitis B and C.
Although animal studies of biologics show they donât affect fertility or hurt the baby, they canât always predict what will happen to humans who take the drugs. Because we donât know how they affect a developing child, pregnant women should use them only if the need is great.
Your doctor will tell you to stop your biologic before surgery. You can start again when your wounds have healed and your chance of getting an infection has passed.
UpToDate: âRituximab: Principles of use and adverse effects in rheumatoid arthritis.â
Angus Worthing, MD, rheumatologist chairman, American College of Rheumatologyâs Government Affairs Committee.
Jonathan Krant, MD, section chief, rheumatology, Adirondack Health Systems.
FDA: âInformation for Consumers .â
Drugs — Real World Outcomes: âComparing Biologic Cost Per Treated Patient Across Indications Among Adult US Managed Care Patients: A Retrospective Cohort Study.â
Pharmacy & Therapeutics: âBiosimilars.â
Annals of Internal Medicine: âBioequivalence of Biosimilar Tumor Necrosis Factor-Î± Inhibitors Compared With Their Reference Biologics: A Systematic Review.â
How Quickly Do Biologics Work
Biologic drugs often take time to start taking effect. Some people with RA feel better after their first treatment, but more commonly, biologic drugs can take a few weeks or months for the initial response. With biologic drugs, its essential to maintain treatment and be patient as the medication takes effect.
I feel like a million bucks after my infusion. I wouldn’t trade that for anything. I can do things, it’s amazing, one myRAteam member said. It really is worth it.
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What Special Precautions Are Needed For Tnf Blockers
TNF blockers suppress the immune system and may increase the risk of getting an infection report any signs or symptoms of an infection, such as a fever, to your doctor immediately. Also report any night sweats or weight loss that occurs during treatment.
You may need vaccinations prior to or during treatment with biologics. Tell your doctor if you have a history of congestive heart failure , cancer or hepatitis.
You will also be tested for tuberculosis before starting a biologic agent.
How Biologics Are Given To Patients
Most biologics are liquid medicines administered to a patient by either:
- Injection under the skin. A patient may give him or herself injections at home. In some cases, a family member or other caregiver may give the injections.
- Infusion into the blood stream. This is typically done in a medical office and can take a few hours.
Pharmaceutical companies are working to develop biologics that can be administered with oral pills. The first of these is tofacitinib, sold as Xeljanz, which was approved by the FDA in 2012.
How often a person takes a biologic varies. In general, infusions may be needed once every 4 to 6 weeks. Injections are usually required every week or two.
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Pick The Right Biologic For You
There are nine biologics available for the treatment of RA. Each type targets a specific inflammatory mechanism of the immune system. Some are given as an injection — a shot under the skin — others are given by infusing it directly into a vein . These drugs can be used alone but are often combined with methotrexate or other RA medications.
|Two doses, two weeks apart about every 6 months|
|Tocilizumab||IV or injection||IV: Once a month injection: Weekly or every other week|
Biologics are used to treat RA when methotrexate has failed. If one biologic doesnât work, your doctor will try another one. It may take some time to find the best drug for you.
The other factor to consider when choosing or switching drugs is side effects. With all of the biologics, you are at increased risk of serious infection.
How Often Do I Take The Biologic
Each biologic has its own schedule or frequency of when it is given. Depending on which biologic you are using, you might need to take it daily, weekly, fortnightly, monthly or only a few times per year. Make sure you have a clear understanding from your rheumatologist or rheumatology nurse of how often you need to take your medication so there is no risk of missing a dose or taking too much. As with any medication, it can only be effective if you take it as directed.
TIP: Taking a medication once a week, fortnightly or monthly can be difficult to remember. Write it in your diary or set an alarm or reminder in your phone/computer to remind you when to take your next dose.
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Be Aware Of The Side Effects With Biologics
The following side effects are rare, but they can be serious or life-threatening:
- Serious skin or lung infections
- Skin cancers
- Serious allergic reactions
Other side effects are less serious: minor infections, headache, and reactions at the injection site. People usually dont change treatments because of these side effects.
Abbvies Oral Jak Inhibitor Rinvoq Ok’d For Ra
In August of 2019 the FDA cleared AbbVie’s Rinvoq , a 15 mg, once-daily oral Janus Associated Kinase inhibitor, for adults with moderate-to-severe rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate .
- In the SELECT Phase 3 studies, roughly 4,400 patients were evaluated. Across all treatment arms in five SELECT studies, Rinvoq met all primary and ranked secondary endpoints.
- In SELECT-COMPARE, 71% of MTX patients treated with Rinvoq 15 mg plus MTX achieved ACR20 compared to 36% treated with placebo plus MTX at week 12.
- Common side effects included upper respiratory tract infections , nausea, cough, and pyrexia .
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What Rheumatoid Arthritis Medications Are In Development
Rheumatoid arthritis treatment is an active area of research. In fact, according to the Pharmaceutical Research and Manufacturers of America, more than 50 drugs for rheumatoid arthritis are in various stages of clinical testing. Many of these are new biologics. Others target histamine receptors and glucocorticoid receptors.
Treating Ra With A Mix
Traditional DMARDs are often used in combination with each other. A traditional DMARD can also be paired with a biologic, but only one biologic is prescribed at a time. If biologics dont help you achieve remission, your doctor may suggest trying a JAK inhibitor instead. If needed, a JAK inhibitor may also be used in combination with a traditional DMARD.
Today, if methotrexate isnt working, doctors are more likely to add on a biologic,” Kaplan says. “In some cases, methotrexate may be stopped if the biologic is working well. If the first biologic isnt working, your doctor may try switching you to a different type of biologic.”
When to start a traditional DMARD, add another, move to a biologic, or try a JAK inhibitor are . No matter what medication youre taking, its important to discuss potential side effects and risks. You may also need regular blood tests to make sure you’re not in danger from certain side effects.
Regardless, these medications are changing the way doctors think about treating RA.
Years ago, I wouldve said its better to have osteoarthritis than rheumatoid arthritis,” Kaplan says. “Today, I can say that there are actually better treatment options for RA.”
Additional reporting by Erica Patino and Kerry Weiss
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Biologic Therapy: Efficacy And Safety
Licensed biologics for RA are shown in .â These drugs, except denosumab, are approved to treat moderate to severe RA that has not responded to conventional DMARDs. The rate of biologic use in clinical practice is rising as more agents become available a recent analysis of US prescribing patterns reported an increase in biologic use from 3% of patients in 1999 to 26% in 2006.
Schedules For Taking Biologics
Biologic drugs are prescribed on a wide range of schedules. Higher doses may be given on a weekly basis at the beginning of treatment and then tapered off to one dose every few weeks. Some biologics are taken only once every eight weeks, after doses are reduced.
I’m on a biologic, infused every six weeks, and personally, it’s been a miracle, said one myRAteam member. I’m now in remission and feel so blessed to feel like my old self!
Talk to your doctor and find out if your biologic treatment allows you any choice in your treatment schedule. Be sure you thoroughly understand your treatment plan. Its important to carefully adhere to the schedule required for the particular biologic drug you are taking.
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Xeljanz: An Oral Ra Treatment
Xeljanz was originally approved in November of 2012 for treatment of patients with moderate-to-severe RA who have had an inadequate response to methotrexate. The extended-release Xeljanz XR was approved in February 2016.
Xeljanz is not considered a biologic, but a small molecule agent that is made with traditional drug manufacturing processes.
Learn more: What is Xeljanz used for and is it a biologic?
Xeljanz was the first oral agent in a new class of drugs called Janus Kinase inhibitors.
- Xeljanz is given twice daily in pill form if you have had an inadequate response to methotrexate the XR form is given once daily.
- It can be used alone or with nonbiologic DMARDs such as methotrexate.
Like biologics, Xeljanz may be associated with serious side effects such as infections, cancer, and stomach or intestinal tears. Discuss the benefits and risks of this therapy with your doctor.
Storing And Handling Biologics
Every biologic will have storage and handling instructions that must be followed, or the drug will lose some or all of its effectiveness. Most biologics should not be:
- Exposed to rapid temperature changes. For example, do not use a heat source to warm up a drug that has been stored in the refrigerator. Let it gradually warm to room temperature before injection.
- Exposed to multiple temperature changes. For example, people are advised against storing a biologic in a refrigerator, then warming it up to room temperature, and then putting it back into the refrigerator for later.
- Shaken. Rapid shaking is usually not necessary and may be harmful.
Why are guidelines like these necessary? Most medications are made up of small, stable moleculesaspirin molecules have just 21 atomsbut biologics are made up of huge molecules with thousands of atoms. The chemical bonds that hold those atoms together are relatively weak, and they can be broken by rapid temperature changes and other factors. A drug will not work as prescribed if too many if its molecules bonds are broken.
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