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Itching and RA

Rheumatoid arthritis has a huge set of issues. The one that perplexed me for a long time was intense itching. The itching in my hands becomes so intense it borders on the edge of being pain. My wrists are included. Sometimes my feet and ankles are involved too. My hands are the worst.  The itching occurs in a random manner.  It doesn’t seem related to anything except it is in proximity to my RA affected joints. Diclofenac topical gel relieves it. Lucky for me.

Why does RA skin itch? What is the itch  connection  to RA? I did a little research on it. This is what I found. There is a lot of discussion on vasculitis, medication side effects, and other itch producing diseases such as eczema. Then there are a few reports that discuss the mechanisms of inflammation seen in RA that trigger the nerve receptors that cause itching.

I think mine is simply caused by the inflammation of rheumatoid arthritis. The itching is random. It is intense. Your itching may be the same or it may have a more complex cause. Put it on your list to discuss with your rheumatologist.

Rheumatoid Arthritis, living close to the edge

We all know that having  rheumatoid arthritis means living with painful joints. Increased inflammatory factors might make you feel sick as well. You may wake up that way every day. You might end your day the same way. You may  live variations. Your life just doesn’t seem like those of the people in the rheumatoid arthritis drug ads that you see on television. Life with RA is not easy. Sometimes it is very hard.

There is the 30% who have no relief from the biologics or any medication.  And then there are people like me who have complex histories. I have  three cancers and a degenerating spine. That means I have been on and off RA drugs many times. The cancer-causing biologic medications are off the table and  lower the number of biologics available to me.

There are those who have  50% relief with their biologic medication. A very few have 70% relief. There are many who have 20% relief with the biologics. It is hard to function with so little relief although it is considered a successful response by the drug companies.  At the present time I am having about 50% relief with  a combination of Orencia and Leflunomide. My flares are shorter and farther apart. Tolerable.

Living with chronic pain is hard. Living with the sick feeling of flares is very hard. Living with the uncertainty of a disease that can be immobilizing without warning is also very hard.  My life is good and I am grateful for it. However, I take issue with those who dance around the difficulties of RA. It is like they are afraid to say life is tough. Saying it is tough doesn’t make it harder but it does give you an appreciation of what you are dealing with when you have rheumatoid arthritis.

What I wanted to say is that I came very close to falling down the slippery slope into into territory that is unforgiving and has no escape. RA requires rising to next challenge with an energy I don’t always know if I have. But deep down I realize that if I don’t rise to the occasion, stretch, push myself, manage more obstacles, swallow more pain, it will be all over. People become tired. Discouraged. Had enough. Live uncertain lives not knowing what is going to happen next.  But. Catch themselves just in time as they start  sliding down the slippery slope. I was lucky.

RA is a chronic disease. Chronic disease means forever. It means being in it for the long haul. It is an elementary  tenet that we need to learn to accept. At the same time, we can respect our strength and our ability to manage the extra demands made on us by a challenging illness that doesn’t have the answers we need. We do the best we can.

RA Biologics affecting your interleukin-6

Tocilizumab (Actemra)

Officially, Actemra is an interleukin-6 receptor antagonist. The drug reduces the impact that Interleukin-6  has on the inflammation process.   Interleukin-6 was discovered and cloned by Japanese immunologist, Tadamitsu Kishimoto who later helped develop the drug Actemra.  In 2010 the FDA approved Actemra for treatment of rheumatoid arthritis.

Actemra is given once every two weeks initially. Depending on the response, it may then be given weekly. The dose is 162mg and it is given  under the skin. Actemra comes in a prefilled syringe, and it also comes in an ACT pen which is an autoinjector. Actemra must be stored under refrigeration until 30 minutes before use.  Actemra may also be given as an infusion which is an IV given over several hours in a medical facility.

  • Blackbox Warning    This warning for Actemra is given for serious, maybe deadly, infections. Infections may include tuberculosis, invasive fungal infections, bacterial, viral, and other infection due to opportunistic pathogens.  A person with a history of diverticulitis should pay attention to new abdominal symptoms, as gastrointestinal perforation has occurred while on Actemra during clinical trials.

Common Side effects   The most common side effects of Actemra are upper respiratory infections (common cold, sinus infection), headache, increased blood pressure and injection site reactions.

Additional serious side effects  

  • Infections must be taken very seriously. A person on an RA biologic will have a compromised immune system.
  • Tuberculosis, if present in the body, may be reactivated. A TB test will reveal the presence of TB. If positive, a person should be treated before starting Actemra.
  • A person with a history of chicken pox should have the new shingles vaccine. Otherwise, there is a risk of shingles.
  • Actemra causes cholesterol levels to rise.Levels should be monitored on a regular basis.

 Pregnancy and lactation            The effects of Actemra on the fetus during pregnancy or on the breast milk are unknown.          

Sarilumab (Kevzara)      

Sarilumab was FDA approved in 2017. It is a human monoclonal antibody produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture.  It  is an IL-6 inhibitor.

It is given by subcutaneous injection either by a prefilled pen or prefilled syringe. The dosage is 200mg given under the skin every two weeks. It should be stored in the refrigerator. It may be stored at room temperature (77⁰F. max) for fourteen days. This is a unique characteristic of the biologics.

Clinical Studies At 52 weeks about 50% patients reached ACR20( 20% improvement); 40% reached ACR 50(50% improvement) ; 25% reached ACR70(70% improvement).

Common Side effects   The most common side effects of Kevzara are upper respiratory infection, urinary tract infection, redness at the injection site.

Precautions The most frequently observed serious infections with Kevzara include pneumonia and cellulitis. A person on Kevzara needs to be monitored for abnormal blood work, gastrointestinal perforation usually associated with diverticulitis, allergic reaction, increased cancer risk.


The black box warning for Sarilumab states  “Serious infections leading to hospitalization or death including bacterial, viral, invasive fungi, and other opportunistic infections have occurred in patients receiving Kevzara.”       

Pregnancy and lactation   The effects of Kevzara on the fetus during pregnancy or in breast milk are unknown.

RA, Nighttime and Cortisol

We all agree that mornings with RA is not easy. Stiffness, pain,  and suffering that feels like it lasts forever. I have learned to manage morning pain well.  I usually wake up about five or six to use the rest room. At that time, I take  pain medication  and I go back to sleep. When I wake up around eight,  the edge has been taken off my discomfort. I  have coffee and read the New York Times for an hour. And then I am good to go.

Some of us with rheumatoid arthritis (RA) experience increased pain at night.  When I am in a flare, I have a hard time sleeping.  My body feels worn  and  ragged. Knuckles, wrists, shoulders, feet, ankles, pelvic girdle, spine. And even my elbows. Nighttime pain is different. It feels heavy. It feels overbearing. It feels endless. It just seems too much. Research has shown that people who experience nocturnal pain have an increased number of swollen, painful joints. They are sicker.

For normal bodies the inflammatory system works to heal wounds and ward off infection at night. This is efficient as the system is not competing with digestion and muscle activity for calories as it would during the day.  

  • First the brain triggers the production of melatonin and prolactin as day turns into night.
  • In turn melatonin and prolactin stimulate the production of inflammatory cytokines such as tumor necrosis factor, TNF,  and interleukin 6.  In a normal body these cytokines do their part in nighttime repair of the body.
  • And then  in the wee hours of the morning,  the normal body produces cortisol.  Cortisol  suppresses these increased cytokines and their inflammatory actions. The body returns to its normal levels of inflammatory cytokines.  
  • A normal person wakes up in the morning refreshed and totally unaware of the nighttime activity.

Those who have RA have an overactive inflammatory system. Their inflammatory cytokines are already elevated.

  • So, when melatonin and prolactin stimulate the production of inflammatory cytokines during their routine nighttime body repair, they are adding to an already increased level of inflammation.
  • But then for those with RA, the normal nighttime cortisol  production  does not increase to control  the additional nighttime inflammatory cytokines and resulting inflammation.
  • Consequently, the nighttime cytokine elevation  does not return to its daytime levels. Inflammation continues.  Pain and stiffness continues into the morning.

Understanding why you might have more nighttime pain doesn’t relieve it. It does give us an understanding of what is happening to us. It gives us a chance to work around our situation. Take extra care. Warm shower. Favorite lotion. Warm herbal tea. Hot chocolate. Good book. Favorite movie. Heated mattress pad.   I am on low dose Medrol in addition to Orencia. I split the dose. I take half in the morning and the other half during the evening.  RA is part of who we are and will always be. Understanding what we have to work with will help us have more satisfying lives.

Targeted biologics for RA Part One Rituxan and Orencia

The following are targeted biologics approved for rheumatoid arthritis.  Targeted means these drugs  dampen a particular  part of the body’s overactive inflammatory process.






Some of the  biologics will not work for you although they work for some other people. Some biologics work for a short time then stop working.  Some biologics work for years then seem to stop working suddenly. Sometimes an insurance company will stop covering certain biologics and insist a patient use a limited selection from their formulary. Some people are affected by the possible, serious side effects of these drugs. These complications happen to somebody so pay attention when your doctor briefly mentions them. Doctors do not know which drugs will work for you. Docs give it their best shot. It is trial and error. There is no system to finding the biologic that will work for you. This is the current medical  scenario. In this article we will discuss Rituxan and Orencia.

Rituxan (Rituximab)

In 1982,  Rituxan was created by Ronald Levy for the express purpose of targeting malignant B cells.  Rituxan affects the CD20, a transmembrane protein present on the surface of all B-cells. In 2006, the  FDA approved Rituxan, manufactured by Genentech, to treat rheumatoid arthritis when used in combination with methotrexate. Before Rituxan can be used, a TNF inhibitor needed to have been tried and failed.  Rituxan works by reducing the inflammatory action of B cells.

  • How drug is given Rituxan is given at a medical facility by infusion(IV) given over 3-5 hours. It is given in two doses two weeks apart. The effect may be sustained for 6 months to a year. It may be repeated four times a year if needed.   
  • Common Side effects:  The most common side effects are infusion reactions, infection, body aches, tiredness, nausea.                                                       
  • BLACK BOX  WARNING  for Rituxan states  “Warning: Fatal infusion reactions, severe mucocutaneous reactions, Hepatitis B virus reactivation and progressive multifocal leukoencephalopathy”
  • Additional serious side effects  Rituxan may cause serious infections, heart problems, kidney problems, stomach, and serious bowel problems.
  • Pregnancy and lactation    A  person should not become pregnant during or for twelve months after the last dose of Rituxan. A woman should not breast feed during or for six months after the last dose of Rituxan.    

Orencia  (Abatacept )

Orencia was developed by the American drug company Bristol-Myers Squibb. It was FDA approved in 2005 for RA. It is a successful biologic that depresses the action of the immune system’s T-cells.

  • How it is given Orencia is administered IV once a month or subcutaneously once a week.
  • Common Side effects    The most common side effects of Orencia are upper respiratory infections, such as common cold and sinus infection, sore throat, headache, and nausea.  
  • Black box warning    There is no black box warning for Orencia. 
  • Serious side  effects              Infection is potentially a serious and common complication of the biologic medications. Orencia depresses the immune system. The most common serious infections involving Orencia are pneumonia and sepsis.  Severe allergic reaction has occurred. Hepatitis B virus reactivation is a possibility. COPD patients on Orencia have more adverse events than those without COPD.    
  • Pregnancy and lactation     Effects of Orencia on the fetus during pregnancy and in breast milk are unknown.

If you would like a copy:

My Journey with Orencia | Mary’s Arthritis (                                                                                                                                                                                                       

More About RA Drug Orencia | Mary’s Arthritis (

Surviving Covid-19 with RA

Those with rheumatoid arthritis are more likely to become ill with covid-19 and they are more likely to be hospitalized or die. In addition, if you are on an immune suppressing biologic your  covid-19 vaccine will only be about 65% effective as opposed to the 95% coverage most people enjoy.

The reason that a third vaccine will soon be available to those who are immune compromised is because those hospitalized with breakthrough infections are from the immune compromised group. This is not a booster shot. It is a third vaccine. Those with RA who are on an immune suppressing biologic will be eligible.

Although those who had RA were included in the vaccine studies, those with RA who were on biologics were disqualified from participating.  So, there was no data on the effect of immune suppressing drugs such as the biologics on the effect of the vaccine. The vaccine is safe for those with RA. Protection from the virus is limited for those on the biologics. It has been found  that those with RA who were on the biologics did not build the antibodies for 95% coverage.

It is important to be immunized. We are thankful to immunizations for the eradication of polio and smallpox. We can also be grateful for the covid-19 vaccine. Those who are vaccinated are not  the ones dying in our hospitals with the virus. Be vaccinated and be safe. When the third vaccine is available, be sure to get it.

It is important to continue to wear masks. They do work. N95 masks are now available to the general public. They offer the best protection.  This is what my son and I use. We also keep hand sanitizer in the car for use when we are out.

Double mask cloth masks. Double mask a cloth mask with a surgical mask. Do not double mask a N95 mask. Wash cloth masks. Avoid touching the front of your mask. Be sure you have a good fit, and you will be fine.

It is wise to be immunized and to wear masks. We have no idea if the people we encounter are immunized or if they are carriers of the virus in their noses.  There are health care workers who haven’t been immunized. The VA requires employees to be immunized. Many corporations are doing the same. This is the trend, and we will all  benefit from it.

RA In the kitchen

In the kitchen with RA

When I was twelve, I road my bike downtown with my mom’s green stamp book in my pocket. I road my bike back home with my first Betty Crocker Cookbook . I still have it. Now I have many recipe resources including the food section in the  NY Times, All recipes and Martha Stewart emails, and King Arthur Baking Recipes.

Now I have Rheumatoid Arthritis and my life has added uphill challenges. Between RA pain and fatigue, doctor visits and drug complications,  ambition frequently descends into the basic mode of  required activity. That activity is as basic as  getting dressed in the morning. Cooking?  Is it really necessary anymore especially when you add the difficulties of RA to the mix?  For some of us, it is. I like to cook. I like the taste of homemade meals. I like the fragrance of baking bread coming from the oven. I enjoy working with my tools and ingredients in my kitchen.  Fresh fruit and veggies. Organic chicken. Cream, buttermilk, unsalted butter.  Working in my kitchen is an activity I would not want to give up despite RA.

RA changes you forever. Change can be quick, but it also can be plodding and subtle. Dangerously so. So slow that you don’t notice the change in how you look at yourself. You don’t  see that you are beginning to think like a victim. It is hard to see when you are sliding into a feeling of helplessness. It is very easy to do  when you have a chronic disease. thinking like a victim or feeling that you are helpless. These are the feelings that send us on a downward spiral. We end up becoming stuck. We don’t want to land there. RA is forever. It won’t go away with time. It is necessary to learn how to live with it. If something in our life doesn’t work,  we need to change it even though it’s not often easy. I enjoy making dinner for my son. Because of my RA, I’ve had to make changes to keep up my routine.  

First, I do keep the freezer stocked with quick meals for those times when we need them. These are meals I buy. Most nights I prefer homemade variety. Tonight, we are having turkey burgers. I made the dough for the buns in my bread machine, shaped them and baked them. Easy for me. You might buy the buns. I mixed and refrigerated the ground turkey ingredients.

 I function best with batching my tasks. All I have left is to cook the burgers and put out condiments. The burgers turned out to be quite good. The recipe is an old one from the NY Times. Later in the afternoon I usually start to feel fatigued.  So, when I make  parts of my dinner earlier in the day, dinner isn’t so hard to make.  

My hands are deformed. Presently, I can use the pointer fingers from each hand to type. For a while I had one pointer finger in use. Hard to type with one finger. I do tend to drop items. And I’m aware of it. I hold on  with  more conscience deliberation when I’m working in the kitchen. Washing the meal prep dishes by hand with hot water running over those very hands feels quite nice.  

It is important that as our circumstances change, we adjust and change to make life better for ourselves. I guess it is called adaptation. It is overwhelming if you look at it that way, but even if we didn’t have RA, we still will have to do it. With RA there is just more to it. Life is harder. Gadgets and time saving tools make life easier and less frustrating.  I have a gadget called a reacher. I used it this morning to get a bag of coffee off a high shelf. Handy.

I love to bake. It is creative. It is even meditative. I found a wonderful book on baking called Flour. My son bought it for me. I learned amazing things like how to make the best ever scones and spicy molasses cookies.  I learned how to weigh my ingredients and found it easier than using measuring cups. I learned  to make crème fraiche and chocolate ganache. These are easy to make in spite of their sophisticated names.  There is a certain joy to it all. It means the good things in our lives are available to us even though we have RA.

TNF inhibitors

The next line in the treatment of RA

TNF inhibitors/TNF blockers are a group of biologic medicines that suppress the body’s response to TNF. TNF (Tumor Necrosis Factor) is a complex protein produced by the white blood cells in response to inflammatory events in the body. Those who have rheumatoid arthritis may be given a TNF inhibitor as part of their therapy.

This is the third article in a series about the treatment options for rheumatoid arthritis. You can download the articles or you can read them on

Many insurance plans may require that you start your therapy with a nonbiologic such as methotrexate (MTX). As troublesome as the side effects are in the beginning, methotrexate has a good success rate. When MTX isn’t enough the doctor may order a combination of methotrexate with sulfasalazine and/or leflunomide. A TNF inhibitor may be the added to the methotrexate.

Although the TNF inhibitors are basically similar, they do have different
properties. If one doesn’t work for you, another might.

Your doctor will order a TB test and will order a shingles vaccine. These diseases are checked out because if these diseases are inactive in your body when you start the TNF inhibitor, they may become active again.

Some of these drugs are given by injection under the skin (subcutaneous, sc).
Drug companies make this process easy with tiny needles and clear instructions.

There are five TNF inhibitors.
• Humira(adalimumab)
• Enbrel(etanercept)
• Remicade(infliximab)
• Simponi(golimumab)
• Cimzia(certolizumab pegol)

Humira is available in a prefilled syringe or a Humira pen of 40mg.
Administered sc every other week. Sometimes the dose is every week. When you sign up for Humira complete, you will be assigned a nurse who can help you optimize your use of Humira. Humira was FDA approved in 2002.

Enbrel was the first TNF inhibitor to be approved by the FDA in 1998; Enbrel is administered sc 50 mg once a week using a prefilled cartridge and reusable auto injector.

Remicade is given in an infusion center by IV over two-hours. There is a series of initial starter doses at baseline, two, and six weeks. Then a maintenance dose is infused every eight weeks. FDA approval 1998.

FDA approval 2009. Simponi is injected sc with a 50mg prefilled
syringe once a month. Simponi aria is given by a 30-minute infusion initially and at four weeks. The maintenance dose is a thirty minute infusion determined by weight every eight weeks.

Cimzia FDA approval 2008. Loading dose two 200mg prefilled syringes sc
initially and at two and four weeks. Maintenance dose 200mg sc every other
week or two 200mg prefilled syringes once a month.

Black box warnings* have been issued for all the TNF inhibitors. These are a few.
• They suppress the immune system and can cause serious infections that
result in death.
• Those who have a history of histoplasmosis, TB or hepatitis B may have
their disease reactivated when using the TNF inhibitors.
• The TNF inhibitors are associated with new onset or worsening of nervous
diseases multiple sclerosis and Guillain-Barre syndrome.
• Heart failure can occur or get worse on the TNF inhibitors.
• Higher rates of cancer have been reported including lymphoma and skin
cancer. Hepatosplenic T cell lymphoma has been seen in young males
who are on TNF inhibitors.

Pregnancy If you are pregnant or planning to be, it is important to discuss your pregnancy with your doctor. Some RA drugs are safer than others during

The big question for the TNF inhibitors as it is for all the biologics is ‘does the
benefit outweigh the risk?’ The TNF inhibitors have made life much better for
many people. It is important to note that they are powerful drugs with powerful side effects. . When you choose to use them in your treatment program for rheumatoid arthritis follow the recommended protocols.

*A black box warning is a very serious warning from the FDA. These things are
happening to RA patients.

RA at eight years

I have been living with rheumatoid arthritis for over eight years now. My onset was dramatic and included a trip to the ER. I was in such severe pain, I was all but immobilized. The ER doc sent me to a rheumatologist. It was the start of the longest relationship I have ever had with a doctor.

I was started on methotrexate pills, prednisone as bridge therapy, and meloxicam. Treatment was complicated with the diagnosis of two cancers both discovered by my rheumatologist during routine tests that first year.

My first cancer was stage three thyroid cancer which required total removal of my thyroid, a complicated surgery followed by systemic radiation treatment that also damaged my salivary glands. On a follow up scan to the one that found the thyroid cancer and ten days after the thyroid cancer surgery, breast cancer was found. A month after the first cancer surgery, I had the second for breast cancer. This was also followed by a series of radiation treatments and then aromatase inhibitors. The last was tamoxifen (which later caused my third cancer).

At the time, the TNF inhibitors would have been the next step. Methotrexate only partially helped me. My doc felt that with my having two cancers, taking the TNF inhibitors would be too risky. So instead, we worked through various combinations of methotrexate with sulfasalazine, leflunomide, and hydroxychloroquine. It was not the answer.

We turned to the biologics. My doc got an exemption from the insurance company to skip the TNF inhibitors and go straight to Rituxan.  It didn’t work. There was not a lot of success until I was given Orencia. I was on 25mg of methotrexate plus the Orencia. I did fine for about a year. I developed a flu and the Orencia stopped working.

After several years, my feet started to feel numb. It wasn’t total numbness. It was patchy. It was enough to make driving my standard transmission mini cooper risky. I just wasn’t sure where my feet were touching the pedals. When the full realization of what was happening hit me, I stopped driving.

Next was a hip replacement. It was a terrible experience but worth it. Next on the plan was Actemra. I had a TB test and the shingles vaccine. My doc also wanted a follow-up to a lumbar scan that showed something in my uterus. A biopsy was scheduled with a gyn doc. She reassured me that it probably was nothing. The biopsy came back as a rare serous uterine cancer which was aggressive and deadly and caused by my breast cancer drug, Tamoxifen.

Fortunately for me the cancer was in the early stages, I was systematically gutted with robotic surgery, poisoned with a summer of chemo leaving me bald and then humiliated with a round of vaginal radiation.  I have a hard time believing that any of my cancers would return as the treatments were so brutal.

Every time we were about to start Actemra something came up. Next was a severe soft tissue necrosis of the radiated tissue of my breast. It took ten months of wound care plus a surgery before I recovered. The culprit was methotrexate. I had been on it for seven years. I was giving myself injections for the last few years. Its thirteenth black box warning was soft tissue necrosis. I no longer have methotrexate as a tool. My flares increased in severity. I am typing with one finger as my hands are almost non-functional.

My RA doc hates steroids more now than ever. With no other solution, I increased the amount of Medrol I was taking as my feet and hands were swelling more and more. Wounds popped open around my lower legs and started draining clear fluid. When my doc saw my legs she put me on Lasix, TED hose, ordered an MRI and cancelled my Medrol.

Turns out Actemra is not recommended for some disorders (diverticulitis, histoplasmosis) that are in my history. The JAC inhibitors can cause cancer. The only drug left was Orencia.

I have been on Orencia for three months. Orencia seems to be the safest of the biologics. It was the only thing left to try and there was no methotrexate to go with it. It is helping. I hope it lasts longer this time. My doc’s toolbox of remedies is nearly empty.  My RA doc and I have had the discussion. She brought up Imuran. It is used for transplant patients and for those with RA.

Palliative support is what I have left. This is me eight years in.

My case seems like an odd one. In some ways it may be. Each of us has a unique story.  The current selection of RA drugs is a big move forward. The biologics are miracle dugs for many. Then there is the third to a half of us who have RA who have mixed to no success with RA drugs.  We are a big problem to the medical community.

Research is ongoing. In the meantime, we need to be assertive with our doctors. We need to understand our treatment plan and expect change when it is not working. We also need to set up our own toolbox that includes a positive mindset and an understanding of RA and of the treatment choices. We have a chronic, progressive disease. It is not going to disappear. Only about 10% of us go into remission. We need to learn to live with it. Hopefully, you have better luck than I have had.  With all my pain and health problems, I am grateful to be alive and every day brings joy to my life.

The Four Non-biologic DMARDs

The Four Non-biologic DMARDs,

Disease Modifying Anti-Rheumatic Drugs,

in common use are


MTX, Rheumatrex, Trexall, Otrexup

Methotrexate has become the most frequently used DMARD in the world.  It reduces the inflammation of RA by suppressing the immune system.  It does not induce remission, but it does slow the progression of joint damage.

Aminopterin, an earlier form of methotrexate was used successfully in a 1951 study to treat RA. In the 1960s methotrexate was extensively studied but its success in treating RA was overshadowed by the popularity of corticosteroids.

In 1972 rheumatologist Rex Hoffmeister reported success with IM injections of methotrexate. After a 15-year study, his 1983 report encouraged other rheumatologists to study the use of methotrexate. After two pivotal studies, the FDA approved methotrexate as a therapy for RA in 1988. By the mid-1990s methotrexate (MTX) becomes the drug of choice for RA.

It usually takes 3-6 weeks to see improvement in symptoms. It takes12 weeks to see the full effect oh MTX.; Folic acid is usually prescribed along with MTX to replace a nutrient depleted during treatment.

Methotrexate is frequently used in combination with other traditional drugs as in triple therapy of methotrexate, sulfasalazine, and hydroxychloroquine. It is also used in combination with most of the biologics.  This combination improves the effectiveness of the drugs.

Gi symptoms such as stomach upset, and diarrhea are quite bothersome for some. These side effects disappear with time. If they don’t, switching to an injection form of MTX instead of a pill will help.

Regular lab work is ordered to monitor any effects on the liver and kidneys.


HCQ, Plaquenil

This was the drug Donald Trump said would cure the covid virus.

Hydroxychloroquine was developed as an anti-malarial drug. It is one of several 4-aminoquinolines. Introduced in 1955, it was found to also reduce symptoms in RA and Lupus. Eventually, it was approved for use in those autoimmune diseases.  For rheumatoid arthritis, it is prescribed for mild, slowly progressive disease.

Plaquenil is also used in combination with other DMARDs for the control of more aggressive RA. For example, it is combined with methotrexate and sulfasalazine to provide a stronger response.

It is important to have regular eye exams as a rare eye disorder can occur while on Hydroxychloquine. The risk can be compounded when a person is also on Tamoxifen for breast cancer.

Hydroxychloroquine is considered safe during pregnancy by the American College of Rheumatology, ACR.



SSZ, Azulfidine

 It is a combination of salicylate (anti-inflammatory)) and sulfa (antibiotic). Sulfasalazine was developed in the 1930’s to treat Rheumatoid Arthritis. It was popular in the 40’s but then fell out of favor with the discovery of the new miracle drug, cortisone. It is now back in favor and is frequently prescribed for RA even though not approved by the FDA for RA use. It has become a substitute for those unable to tolerate methotrexate.


LEF, Arava

Leflunomide is a DMARD and immunosuppressant.  The usual dose is 20mg. It was approved in 1998 for the treatment of RA.  Leflunomide is an alternative when methotrexate is not tolerated.  Alternately, it may also be combined with methotrexate. The half-life is long. Onset takes 4-8 weeks. Side effects: GI upsets, diarrhea. Hair loss in 10% of those on Arava.  

Leflunomide is contraindicated in pregnancy. Leflunomide is capable of damaging a fetus.   For a couple planning pregnancy, it is necessary for both partners to take cholestyramine to eliminate the active metabolites of leflunomide completely.

My view

I have been on all these drugs at one time or another. I was on methotrexate for seven years. The last few years I was on the injectable form. Initially, I did have a problem with diarrhea, but it passed. It helped me about 50%. Significant. I had to stop it when I developed necrosis in radiated breast tissue.

My RA treatment is complicated by my history of three different cancers. My symptoms have worsened. I have used Medrol to see me through until Orencia starts helping which it is at three months. Medrol has been a life saver but it has its own problems.

Hydroxychloquine was not helpful either alone or in combination with other drugs. Sulfasalazine made me sick. I think the sulfa didn’t agree with me. Leflunomide was no help either.


Next topic will be on the TNF inhibitors. This class of biologic drugs is usually the first biologic giver to a patient.

Reliable resources

American College of Rheumatology                

American College of Rheumatology

Johns Hopkins Arthritis Center                             

Johns Hopkins Arthritis Center

Creaky Joints                          

CreakyJoints – Arthritis Support, Education, Advocacy and Research

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