Will New Medication Guidelines For Rheumatoid Arthritis Improve Patient Satisfaction With Treatment?

By Kathleen Hoffman, PhD, MSPH

Despite the advances and diversification of disease modifying antirheumatic drugs (DMARDs) to treat rheumatoid arthritis (RA), a recent report surveying current RA patients showed that the majority are not satisfied with their treatment experience. In a study of 258 patients, all of whom were taking at least 1 DMARD, only 26% were satisfied with the results of their treatment. In fact, 43% reported taking pain relievers daily or almost daily, and 44% said that they were currently having a flare.¹

Rheumatoid arthritis is a chronic disease that causes abnormal inflammation. While it primarily affects the joints, it can create inflammation in other organ systems.² It is different from the more common osteoarthritis in that RA is an autoimmune disorder, not the result of wear and tear on the cartilage.³ RA affects about 1.3 million U.S. citizens, or 0.6% of the population.⁴

I was diagnosed with seropositive RA in the 1970s. Back then none of the DMARDs like [drug name] were used to treat RA. Nor were any of the biologics available. The first biologics didn’t come on the market, till around 2000. Despite a healthy diet, no processed or junk foods, eliminating certain foods, my RA progressed and damaged joints throughout my body.

Hi everyone, Im [name] & new here . I was diagnosed with RA early this year, id symptoms on and off for roughly 10 months before that. I ve had 3 [brand name] steroid shots & tried [DMARD] but got a bad virus and uti and eye infection and was ill gor a month and didnt like it . My Rhumy then put me on [DMARD] which ive been stalling to take as i wanted to try the natural route taking Botswellia, Curcumin , Asheaghanda , Ginger, probiotics, & Vit B complex , ive been taking this supplement combination for only 5 days but my concern is … Do all these herbal only reduce inflammation? And if so does that mean your immune system would continue to attack your body?

One of the difficulties in treating rheumatoid arthritis might be related to the number of treatment alternatives rheumatologists have to consider. Take the increasing number of available drugs plus the variability in individual cases, and multiply them by the preferences of physicians and experiences of patients. Add to it that patients also take NSAIDs and are sometimes prescribed steroids to manage symptoms.⁵ Fortunately, while there is no one “best route” for managing each case, there is some basis for agreement.

Recognizing this ongoing “evolution of medical knowledge, technology, and practice,” the American College of Rheumatology (ACR) reviews and revises its guidelines for the medical treatment of RA every five years. The latest version was released in draft form in November 2020 and published in Arthritis Care and Research in July 2021.⁶

The review panel poses a set of questions to resolve, systematically reviews the literature, and votes on a set of recommendations based on the evidence. The recommendations are further qualified based on the panel’s agreements on the evidence into categories of a “strong” or “conditional” guideline. Acknowledging the importance of patient experience, the voting panel of clinicians is advised by a patient panel regarding proposed recommendations.⁵

This year’s report gives guidelines on the use of DMARDs, glucocorticoids, and treatment of some high-risk cases of RA often encountered in clinical practice.
DMARDs are the cornerstone of RA treatment. There are three types of DMARDs:

• csDMARDs (conventional synthetic): Methotrexate is the oldest; others include leflunomide and sulfasalazine.
• bDMARDs (biologics): bDMARDs target b cells (rituximab), t-cells (abatacept); interleukin-6 (tocilizumab); and inhibit tumor necrosis factor TNF (adalimumab and etanercept).
• tsDMARDs (targeted synthetic): tsDMARDs are Janus kinase (JAK) inhibitors (filgotinib).

This update recommends an initial trial of hydroxychloroquine or sulfasalazine before trying methotrexate for treatment-naive patients with low disease activity. The 2015 guidelines recommended csDMARD monotherapy, preferably with methotrexate, for patients with both low and moderate/high disease activity.⁵

This report finds that, for the initial treatment in DMARD-naive patients with moderate-to-high disease activity, methotrexate monotherapy is strongly recommended over:

• Hydroxychloroquine or sulfasalazine
• bDMARD or tsDMARD monotherapy
• Combination of methotrexate plus a non–TNF inhibitor bDMARD or tsDMARD<⁵/li>

Methotrexate monotherapy is conditionally recommended over:

• Leflunomide
• Dual or triple csDMARD therapy
• Methotrexate plus a TNF inhibitor⁵

Methotrexate monotherapy is strongly recommended over bDMARD or tsDMARD monotherapy for DMARD-naive patients with moderate-to-high disease activity as well because of low cost, comparative safety, and the ease for patients of taking one drug instead of several per day with different dose schedules. They prefer oral methotrexate over injectable for the same reasons. However, some patients may want a csDMARD combination because of the possibility of obtaining a better response to the treatment.⁵

For those who have had treatment with other csDMARDs (not methotrexate) with moderate to high disease activity, they are recommending methotrexate again — not in combination with a bDMARD or tsDMARD. The biologics and tsDMARD therapies do have a place in treatment: The panel conditionally recommends them over triple therapy (i.e., adding sulfasalazine and hydroxychloroquine), but not until patients have maximized doses of methotrexate without reaching target.⁵

This recommendation was a matter of considerable debate, with panelists in favor of a bDMARD or tsDMARD earlier “because of the more rapid onset of benefit.” The patient panel also pointed out the importance of having a rapid benefit after already enduring an inadequate response from methotrexate.⁵

They don’t exclude triple therapy in csDMARD modification: despite its limitations in tolerability and durability, “…triple therapy may be preferred in lower resource settings as well as in patients with specific comorbidities for whom triple therapy may be associated with significantly less risk of adverse events.”⁵

While acknowledging that patients themselves want to be off medication when they are feeling well, the guidelines also caution against discontinuing DMARDs — even when the patient is stable for over six months — because of the risk of recurrence. In this regard, the recommendations are:

• Continuation of all DMARDs at their current dose is conditionally recommended over a dose reduction of a DMARD.
• Dose reduction is conditionally recommended over gradual discontinuation of a DMARD.
• Gradual discontinuation is conditionally recommended over abrupt discontinuation of a DMARD.⁵

These recommendations are all conditional because the certainty of the evidence is low. The preference would be for the patient to continue to take DMARDs.

The report strongly recommends against prescribing glucocorticoids — like cortisone and prednisone — on a long-term basis when initiating DMARD treatment. While they acknowledge that patients appreciate the relief the steroids give, expecting long-term relief creates a dependency that is hard to break even in the face of toxicities.⁵

An Inspire member described the complexity facing taking even recommended medications:

I’ve taken MTX for one week, side effects were worst the day after (I took it at night). I took a pill last week but hopefully can start injection this week, which is supposed to have fewer side effects. I almost burst into tears in the rheumy’s office when she said I had to take MTX [methotrexate]for 3 months before we could try something else due to my insurance. It helped that she said that most of the side effects you read about are with the chemotherapy dose, not the low dose we take for autoimmune diseases. …My career requires manual dexterity, and my hands are getting bad very quickly, so I didn’t want to wait to see if something else might work…I fully understand why someone else wouldn’t want to take the medication route without trying something else first.

Given the dissatisfaction with treatments found in the patient survey, it is going to be a challenge to recommend a well-known older drug and withholding steroids in the face of patient suffering. The guidelines recommend that clinicians and patients take a “treat-to-target” approach to this difficult disease, and adjust treatments based on agreed-upon targets measured at regular intervals.

The implication being, until a cure is found, the emphasis should be on managing patient expectations as well as trying to manage the disease itself.

On October 14, 2021 at 2 pm ET, Inspire is holding a webinar titled, “Leveraging real world patient generated data to build clinical, commercial, and medical strategies.” Be sure to sign up for this informative event!