Why Rheumatoid Arthritis Often Defies Drugs (& What Else you Can Try)

Arthritis is the umbrella term for a cluster of joint diseases involving inflammation of the joints, hence “arthr-” (joint) “-itis” (suffix used to denote inflammation). These are mostly, but not all, autoimmune diseases, in which the body’s immune system mistakenly attacks our own joints.

Rheumatoid arthritis is one of those. Indeed, it’s the common of the autoimmune forms of arthritis. Some quick facts:

• Approximately one third of people stop work within two years of its onset, and this increases thereafter.
• It affects a little under 1% of the global population, but the older we get, the more likely it becomes
• Early onset of rheumatoid arthritis is most likely to show up around the age of 50 (but it can show up at any age)
• However, incidence (not onset) of rheumatoid arthritis peaks in the 70s age bracket
• It is 2–4 times more common in women than in men

When meds don’t work (and why)

There are three main kinds:

• Pain relief (always hit-and-miss, unless going for literal anaesthetic)
• Anti-inflammatory (can rarely go too far wrong, although some can give different problems)
• Arthritis-specific, which are usually also anti-inflammatory in their own way, but deserve a special mention

For example, a lot of arthritis medications act via the interleukin-17 pathways.

However, researchers (Dr. Martina Zoccheddu et al.) found that in rheumatoid arthritis, the immune cells that normally make IL-17 gradually stop producing it, which explains why IL-17-targeted drugs lose effectiveness as the disease progresses.

Even worse, once these cells stop making IL-17, they turn into aggressive forms that can still sustain joint inflammation independently of IL-17, meaning that the meds can end up doing more harm than good in the long-run!

To quote Dr. Joyce So when asked about this,

❝This important new insight contributes to shifting the paradigm of how we understand rheumatoid arthritis progression and why IL-17 treatments haven’t worked as well as expected. Only with a precise understanding of the biological mechanisms of disease can effective, precision therapies be developed.

In the meantime, clinicians can help patients in early or presymptomatic stages make the most of treatments that may lose effectiveness over time.❞

You can find the paper itself, here: TH17 cells converted into exTH17 cells sustain rheumatoid-like IL-17–independent inflammatory arthritis

About those early or presymptomatic stages…

Another team of researchers (Dr. Marla Glass et al.) recently found that rheumatoid arthritis begins long before pain, with people who carry a particular kind of antibodies showing body-wide inflammation, malfunctioning immune cells, and gene-regulation changes for at least seven years before symptoms show up.

In other words, the immune system is behaving as though rheumatoid arthritis is already active, and so, in a way, arguably it is already active.

This is all going on in ways that you wouldn’t see without doing blood tests, though.

For example (we will quote these key points directly):

• Widespread inflammation: The researchers observed that people at risk for RA already showed signs of systemic inflammation throughout the body. This inflammation was not limited to the joints. Instead, it resembled the body-wide inflammatory pattern commonly seen in individuals with active RA.
• Immune cell dysfunction: Multiple immune cell types showed unusual behavior.
• B cells, which normally create protective antibodies, were found in a heightened pro-inflammatory state.
• T helper cells, especially those similar to Tfh17 cells, had expanded far beyond typical levels. These cells help coordinate immune responses, including the creation of autoantibodies (antibodies that attack the body’s own tissues). Their expansion helps explain why the immune system begins targeting healthy tissue.
• Cellular reprogramming: One of the most striking discoveries was that even “naive” T cells, which have not yet encountered pathogens, showed epigenetic changes. Although their DNA sequence remained intact, the regulation of their genes had shifted. This altered gene activity suggests these cells were being reprogrammed before encountering any threats.
• Joint-like inflammation detected in blood: The team also found that monocytes (a type of white blood cell) circulating in the bloodstream were producing high amounts of inflammatory molecules. Remarkably, these cells closely resembled the macrophages typically found in the inflamed joints of RA patients, indicating that the immune system was already setting the stage for joint inflammation.

You can find this paper itself, here: Progression to rheumatoid arthritis in at-risk individuals is defined by systemic inflammation and by T and B cell dysregulation

What that means in practical terms

If you get a rheumatoid arthritis diagnosis, even if it feels like you got it quickly, chances are you’ve technically had it for a long time already.

So, if you don’t have such a diagnosis, it is good to behave as though you did (aside from the pain relief component, of course, if you have no pain), because honestly, the advice for managing arthritis is very good advice anyway, since it tends to target improving joint health and reducing chronic inflammation.

With that in mind, do check out:

• How to Prevent (or Reduce) Inflammation
• Five Supplements That Actually Work Vs Arthritis

And for a very deep dive into excellent exercise vs arthritis, see:

Yoga Therapy for Arthritis – by Dr. Steffany Moonaz & Erin Byron

…which is a particularly good book, much better than most of its kind, because:

• One of the problems with arthritis and exercise is that arthritis can often impede exercise.
• Another of the problems with arthritis and exercise is that some kinds of exercise can exacerbate arthritis.

This book deals with both of those issues, by providing yoga specifically tailored to living with arthritis. Indeed, the first-listed author’s PhD in public health was the result of 8 years of study developing an evidence-based yoga program for people with arthritis, including osteoarthritis and rheumatoid arthritis.

The authors take the view that arthritis is a whole-person disease (i.e. it affects all parts of you), and so addressing it requires a whole-person approach, which is what this book delivers, and so that’s why we highly recommend it.

And if you do have the pain component already…

We’ve written quite a bit about pain management, including:

• Before You Reach For That Tylenol…
• How To Stop Pain Spreading
• How To Dial Down Your Pain
• Managing Chronic Pain (Realistically!)
• Get The Right Help For Your Pain
• The 7 Approaches To Pain Management
• Science-Based Alternative Pain Relief (When Painkillers Aren’t Helping, These Things Might)

Take care!