Levels of Treatment Response in Rheumatoid Arthritis

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“Present treatment strategies for rheumatoid arthritis include use of disease-modifying antirheumatic drugs, but a minority of patients achieve a good response.”[1]

Most of what people know about treatments for Rheumatoid Disease has been communicated by pharmaceutical companies through drug reps, or in press releases or direct to consumer advertisements. The experiences of patients, and the results of clinical trials present a different impression.

There is wide variation in response rates to current Rheumatoid Arthritis treatments. Medications are highly effective at reducing symptoms or slowing progression of damage in a minority of patients with moderate to severe disease who are prescribed disease-modifying anti-rheumatic drugs (DMARDs) or Biologics, but a majority experience limited response (about one-third are non-responders and nearly 30% have only twenty percent improvement).[1, 2] In moderately to severely active disease, DMARDs such as methotrexate have lower efficacy rates than Biologics.[3, 4, 5] Biologic DMARDs are not indicated for people with mildly active disease, who tend to have a more adequate response to weaker DMARDs. People with Rheumatoid Disease (PRD) frequently change medications when the disease becomes more active or treatments become less effective over time, in part due to the production of anti-treatment antibodies. Most PRD require symptom-relieving medicines for symptoms that remain in spite of treatment.[6, 7] There is not yet a cure for Rheumatoid Disease, and there remains a great need for new treatments due to insufficient response rates and efficacy reducing over time.

Five things to consider about treatment responses

1) Combination therapies are most effective.

Studies have shown Biologics combined with traditional DMARDs are more effective, [8, 9] and “triple therapy” with a combination of DMARDs is also more effective than a single therapy.[10]

2) Different treatments are more effective in particular patients.

In spite of numerous comparison studies and a ridiculous attempt by Consumer Reports[11], conclusions cannot be drawn as to which RA treatments are most effective since efficacy varies so much between PRD. A Biologic or other DMARD may be ineffective in one person’s disease, while bringing near remission of symptoms in another. It is not yet possible to predict which treatments are more likely to be effective in particular PRD, but efforts are being made to learn how to do so. Since over time the disease can also change its behavior in the same patient, a medication can also lose efficacy (see above).

3) RA treatments often stop working after a period of weeks, months, or years.

Doses or combinations of medications often need to be adjusted when they become less effective and PRD experience more disease symptoms. It is difficult to know how much of this this is due to an increase in disease activity or to the loss of efficacy of medications. Medications can lose efficacy because of changes in the patient’s particular disease or because of development of antibodies against the medications.

4) Patients may consider a total experience of disease impact and all medication effects in treatment decisions.

Patients may consider what I call “all-disease-impact” (ADA) when estimating their level of disease activity. This includes extra-articular disease symptoms like fatigue, Sjögren’s syndrome, and, shortness of breath, as well as “consequences of physical activity.”[12] Likewise, PRD view medications in light of their complete experience, including side effects, injection site reactions, direct financial cost, method of administration, and medication efficacy. According to tens of thousands of patient comments on this site, RD pain or discomfort is often severe[13, 14], and one study found it was “worse than death.”[15] Pain and other disease consequences are often harsh enough that people are willing to endure unpleasant medication side effects in an attempt to moderate the disease, and may even withhold side effect reports from their doctors.[16] However, treatments that bring inadequate response may be abandoned based on the equation of a patient’s total experience.

5) Very early treatment is most effective.

Studies in very early rheumatoid disease have shown much improved treatment response rates.[17] However, such trials also include the use of corticosteroids to reduce inflammation, a practice that is avoided by many rheumatologists in the field. Conversely, a minority of PRD with long-standing disease achieve good clinical response or remission with treatment.[18]

MORE INFORMATION

7 Key Facts on Rheumatoid Arthritis Medications
Efficacy of Xeljanz, Biologics, & DMARDs in Rheumatoid Disease
10 Answers to “When Do I Start a Biologic Treatment for Rheumatoid Arthritis?”
Significant Numbers of RA Patients Don’t Receive Recommended Care

FOOTNOTES

1 Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, Kincaid W, Porter D. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004 Jul 17-23 [cited 2013 25];364(9430):263-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15262104

2 Young, K. Efficacy of Xeljanz, biologics, & DMARDs in rheumatoid disease. Rheumatoid Arthritis Warrior [Internet]. 2013 May 13 [cited 2013 May 28]. Available from: http://rawarrior.com/efficacy-of-xeljanz-biologics-dmards-in-rheumatoid-disease/

3 Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Wasko MC, Moreland LW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: Two-year radiographic and clinical outcomes. Arthritis Rheum [Internet]. 2002 Jun [cited 2013 Sep 22];46(6):1443–1450. Available from: http://onlinelibrary.wiley.com/doi/10.1002/art.10308/full

4 Linde L,. Hetland ML, Østergaard M. Drug survival and reasons for discontinuation of intramuscular methotrexate: a study of 212 consecutive patients switching from oral methotrexate. Scand J Rheumatol [Internet]. 2006 [cited 2013 Sep 22];35(2):102-106. Available from: http://informahealthcare.com/doi/full/10.1080/03009740500343294

5 Young K. A methotrexate alternative for rheumatoid arthritis? Rheumatoid Arthritis Warrior. 2011 Aug 15 [cited 2013 Sep 22]. Available from: http://rawarrior.com/a-methotrexate-alternative-for-rheumatoid-arthritis/

6 Strand V, Emery P, Fleming S, Griffin C. The impact of rheumatoid arthritis (RA) on women: focus on pain, productivity and relationships [abstract]. Arthritis Rheum [Internet]. 2010 [cited 2013 Mar 24];62 Suppl 10:1063. Available from: http://www.blackwellpublishing.com/acrmeeting/abstract.asp?MeetingID=774&id=89712 doi: 10.1002/art.288302012

7 Rheumatoid Patient Foundation [Internet]. Unmasking rheumatoid disease: the patient experience of rheumatoid arthritis. A white paper from the Rheumatoid Patient Foundation. 2013 Apr 20. Cited 2013 Mar 28].  Available from: http://rheum4us.org/wp-content/uploads/2013/04/Unmasking-Rheumatoid-Disease-The-Patient-Experience-of-Rheumatoid-Arthritis-White-Paper.pdf

8 Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum [Internet]. 2006 Jan [cited 2013 Sep 22];54(1):26–37. Available from: http://onlinelibrary.wiley.com/doi/10.1002/art.21519/full

9 Pope JE, Haraoui B, Thorne C, Vieira A, Poulin-Costello M, Keystone EC. The Canadian methotrexate and etanercept outcome study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis. Ann Rheum Dis [Internet]. 2013 Aug 26 [cited 2013 Sep 22];0:1–8. Available from: http://ard.bmj.com/content/early/2013/08/26/annrheumdis-2013-203684.full

10 Dale J, Alcom N, Capell H, Madhok R, Lie D. Combination therapy for rheumatoid arthritis: Triple therapy. Nat Clin Pract Rheumatol CME. 2007 [cited 2013 Sep 22];3(8):450-458. Available from: http://www.medscape.org/viewarticle/560135_4

11 Young K. Consumer Reports’ absurd best buy rheumatoid arthritis drug list. Rheumatoid Arthritis Warrior [Internet]. 2012 May 12 [cited 2013 May 31]. Available from: http://rawarrior.com/consumer-reports-absurd-best-buy-rheumatoid-arthritis-drug-list/

12 Young K. Abstract poster to be published 10/29/13

13 Responses to “Does Rheumatoid Arthritis Pain Really Hurt That Much?” Rheumatoid Arthritis Warrior. 2012 Feb [cited 2013 Sep 22]. Available from: http://rawarrior.com/does-rheumatoid-arthritis-pain-really-hurt-that-much/?show=comments

14 Responses to “Do Rheumatoid Arthritis Patients Have a Low Pain Threshold?” Rheumatoid Arthritis Warrior. 2012 Feb [cited 2013 Sep 22]. Available from: http://rawarrior.com/do-rheumatoid-arthritis-patients-have-a-low-pain-threshold/?show=comments

15 Gaujoux-Viala C, Fautrel B, Guillemin F, Flipo RM, Bourgeois P, Rat AC. Who are the patients with early arthritis with worse than death scores on the EQ-5D? Results from the ESPOIR cohort. (Oxford) Rheumatology [Internet]. 2012 Oct 22 [cite 2013 Sep 22];52(5):832-838. Available from: http://rheumatology.oxfordjournals.org/content/52/5/832.long

16 Arkell P, Ryan S, Brownfield A, Cadwgan A, Packham J. Patient experiences, attitudes and expectations towards receiving information about anti-TNF medication – “It could give me two heads and I’d still try it!” BMC Musculoskel Dis [Internet]. 2013 [cited 2013 Sep 22];14:165. Available from: http://www.biomedcentral.com/1471-2474/14/165

17 van den Broek M, Lems WF, Allaart CF. BeSt practice: the success of early-targeted treatment in rheumatoid arthritis. Clin Exp Rheumatol 2012 [cited 2013 Sep 22]; 30 (Suppl. 69):S35-S38. Available from: http://www.clinexprheumatol.org/article.asp?a=6142

18 Atzeni F,  Antivallea M, Pallavicinib FB, Caporalib R, Bazzanic C, Gorlac R, Favallid EN, Marchesonid A, Sarzi-Puttinia P. Predicting response to anti-TNF treatment in rheumatoid arthritis patients. Autoimmun Rev [Internet]. 2009 Mar [cited 2013 Sep 22];8(5):431–437. Available from: http://www.sciencedirect.com.ezproxy.net.ucf.edu/science/article/pii/S1568997209000093

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