The RA (Rheumatoid arthritis) treatment guidelines published here have been prepared by the ACR (American College of Rheumatology). So far these are the latest published guidelines that cover the treatment aspect of Rheumatoid Arthritis. These RA treatment guidelines are expected to be updated in early 2020.

The ACR RA treatment guidelines - What's new?

The RA treatment guidelines focus on four major areas:

• Treatment recommendations in patients with early Rheumatoid arthritis
• Treatment recommendations in patients with established Rheumatoid arthritis
• Treatment recommendations in high-risk subgroups with RA
• Vaccination recommendations in patients.

Before discussing the ACR treatment guidelines, let's briefly define some key terms:

• An adult patient with RA:

  • Adults,18 years of age or older, meeting the ACR RA classification criteria (1987 or 2010 revised criteria).

• Early Rheumatoid Arthritis:

  • RA with a duration of disease or symptoms of less than 6 months, where the “duration” denotes the length of time the patient has had symptoms/ disease, not the length of time since the diagnosis of Rheumatoid Arthritis.

• Established Rheumatoid Arthritis:

  • Rheumatoid Arthritis with a duration of disease/ symptoms of 6 months or more or meeting 1987 ACR Rheumatoid Arthritis classification criteria.

• Rheumatoid Arthritis remission:

  • Remission is defined as a tender joint count, swollen joint count, C-reactive protein level (mg/dl), and patient global assessment of less than 1 each or a Simplified DAS of less than 3.3 (151), 1 of 6 ACR-endorsed disease activity measures.

• Active hepatitis B infection:

  • Hepatitis B surface antigen-positive, hepatitis B surface antibody negative, hepatitis B core antibody total positive (less important), AST/ALT typically increased, HBV DNA positive (if checked).

• Hepatitis C infection:

  • Patients with a positive anti-HCV antibody test, positive HCV RNA PCR, and raised AST/ALT.

• TNF biologics:

  • Adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab

• Non-TNF biologics:

  • Abatacept, rituximab, or tocilizumab (excludes anakinra because of its infrequent use).

• Low dose glucocorticoids:

  • </ = 10 mg/day of prednisone (or equivalent).

• High dose glucocorticoids:

  • Patients on more than 10 mg/day of prednisone (or equivalent) and up to 60 mg/day with a rapid taper (tapered in six weeks to 7.5 mg/day)

• Short-term glucocorticoids:

  • < 3 month treatment

Revision of the 2010 ACR/EULAR criteria for diagnosing Rheumatoid arthritis.

[caption id="attachment_9462" align="aligncenter" width="577"] ACR/ EULAR classification criteria[/caption]

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Instruments used to measure disease activity score in Rheumatoid Arthritis:

Instruments that measure RA disease activity and define remission
Reference	Threshold of disease activity
Patient Activity Scale (PAS) or PASII (range 0–10)	Remission: 0–0.25 Low activity: > 0.25 – 3.7 Moderate activity: > 3.7 to < 8.0 High activity: >/= 8.0
Routine Assessment of Patient Index Data 3 (RAPID3) (range 0–10)	Remission: 0–1.0 Low activity: > 1.0–2.0 Moderate activity: > 2.0 –4.0 High activity: > 4.0 – 10
Clinical Disease Activity Index (CDAI) (range 0–76.0)	Remission: </= 2.8 Low activity: > 2.8 – 10.0 Moderate activity: > 10.0–22.0 High activity: > 22
Disease Activity Score (DAS) 28 erythrocyte sedimentation rate (ESR) (range 0–9.4)	Remission: < 2.6 Low activity: >/= 2.6 to < 3.2 Moderate activity: > 3.2 to </= 5.1 High activity: > 5.1
Simplified Disease Activity Index (SDAI) (range 0–86.0)	Remission: </= 3.3 Low activity: > 3.3 to </= 11.0 Moderate activity: > 11.0 to </= 26 High activity: > 26

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Recommendations for patients with symptomatic early RA

1. Physicians must use a treat to target strategy rather than a non-targeted approach, regardless of the disease activity level (Low).

2. If the rheumatoid arthritis disease activity is low, in patients who have never taken DMARD therapy

   • Use DMARD monotherapy (Methotrexate preferred) over double therapy.

   • Use DMARD monotherapy (Methotrexate preferred) over triple therapy.

3. If the RA disease activity is moderate or high, in patients who have never taken DMARD therapy:

   • Use DMARD monotherapy over double therapy

   • Use DMARD monotherapy over triple therapy

4. If the disease activity remains high despite DMARDs monotherapy (with or without glucocorticoids), use combination DMARDs, or TNF inhibitors or a non-TNF biologics (all choices with or without methotrexate) rather than continuing DMARD monotherapy.

5. If the disease activity remains moderate or high despite DMARDs:

   • Use TNF inhibitor monotherapy over tofacitinib monotherapy

   • Use a TNF inhibitor + methotrexate over tofacitinib + methotrexate

6. If the disease activity remains moderate or high despite DMARD or biologic therapies, add low dose glucocorticoids

7. If disease flares, add short term glucocorticoids at the lowest possible dose and for the shortest possible time.

[caption id="attachment_9463" align="aligncenter" width="505"] Treatment algorithm for treatment-naive patients[/caption]

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Recommendations for patients with established RA

1. Physicians must use a treat to target strategy rather than a non-targeted approach regardless of the disease activity level (Low).

2. If the rheumatoid arthritis disease activity is low, in patients who have never taken a DMARD, DMARD monotherapy (Methotrexate preferred ) should be used rather than a TNF inhibitor.

3. If the RA disease activity is moderate or high, in patients who have never taken a DMARD

   1. Use DMARD monotherapy (Methotrexate preferred) over tofacitinib.

   2. Use DMARD monotherapy (Methotrexate preferred) over combination DMARD therapy.

4. If the disease activity is moderate or high, despite DMARD monotherapy, use combination traditional DMARDs or add a TNF inhibitor or a non-TNF biologic or tofacitinib (All choices with or without methotrexate), rather than continuing DMARD monotherapy alone

5. If the disease activity is moderate or high, despite TNF inhibitor therapy in patients who are currently not on DMARDs, add one or two DMARDs to TNF inhibitor therapy rather than continuing TNF inhibitor therapy alone.

6. If the rheumatoid arthritis disease activity is moderate or high, despite the use of a single TNF inhibitor drug:

   • Use a non-TNF inhibitor therapy, with or without methotrexate, rather than adding another TNF inhibitor with or without methotrexate

   • Use a non-TNF biologic therapy, with or without methotrexate, rather than tofacitinib with or without methotrexate

7. If the disease activity is moderate or high, despite the use of single non-TNF biologic, use another non-TNF biologic, with or without methotrexate, over tofacitinib, with or without methotrexate.

8. If the disease activity is moderate or high, despite the use of multiple (2+) sequential TNF inhibitor therapies, first use a non-TNF biologic, with or without methotrexate, over another TNFi or tofacitinib (with or without methotrexate).

9. If the disease activity is moderate or high, despite the use of multiple TNFi therapies, use tofacitinib with or without methotrexate over another TNF inhibitor, with or without methotrexate, if the use of non-TNF biologic is not an option.

10. If the disease activity remains moderate or high, despite the use of at least one TNF inhibitor and at least one non-TNF biologic:

    1. First use another non-TNF biologic, with or without methotrexate, over tofacitinib

    2. If the disease activity is moderate or high, use tofacitinib, with or without methotrexate, over another TNF inhibitor.

11. If the disease activity remains moderate or high, despite the use of DMARD, TNF inhibitor, or non-TNF biologic therapy, add a short term, low dose glucocorticoid therapy.

12. Short-term glucocorticoid therapy may be added (the lowest possible dose for the shortest possible time) in patients with a disease flare despite DMARD, TNF inhibitor, or non-TNF biologic therapy.

13. If the patient is in remission:

    1. Taper DMARD therapy

    2. Taper TNF, non-TNF biologic, or tofacitinib

14. If the disease activity is low:

    1. Continue DMARD therapy

    2. Continue TNFi, Non-TNF biologic, or tofacitinib rather than discontinuing them

15. Do not discontinue all rheumatoid arthritis therapies if the patient is in remission.

[caption id="attachment_9464" align="aligncenter" width="606"] Recommended treatment for patients with established Rheumatoid Arthritis.[/caption]

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Treatment recommendations in high-risk subgroups:

1. Congestive heart failure:

   1. CHF:

      • Use combination disease-modifying agents, or non-TNF biologics, or tofacitinib, rather than TNF inhibitor therapy.

   2. CHF worsening on current TNFi therapy:

      • Use combination DMARDs, or non-TNF biologics, or tofacitinib, over another TNFi

2. Hepatitis B:

   • Active Hepatitis B infection and receiving or received effective antiviral therapy:

     • Same recommendations as in patients without this condition

3. Hepatitis C:

   • Hepatitis C infection and receiving/ received antiviral therapy:

     • Same recommendations as in patients without this condition

   • Hepatitis C infection and not receiving or requiring effective antiviral therapy:

     • use DMARD therapy over TNFi

4. Past history of treated or untreated malignancy:

   • Previously treated skin cancer (Melanoma or non-melanoma):

     • Use DMARD over biologic in melanoma

     • Use DMARD over Tofacitinib in melanoma

     • Use DMARD over biologic in non-melanoma

     • Use DMARD over Tofacitinib in non-melanoma

   • Previously treated lymphoproliferative disorder:

     • Use rituximab over TNFi

   • Previously treated lymphoproliferative disorder:

     • Use a combination of a disease-modifying agent or abatacept or tocilizumab rather than a TNF inhibitor

   • Previously treated solid organ malignancy:

     • Same recommendations as in patients without this condition

5. Pervious Serious infection:

   • Use combination DMARD over TNFi

     • Use abatacept over TNFi

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Vaccination recommendations in RA:

	Killed vaccines			Recombinant vaccine	Live attenuated vaccine
	Pneumococcal	Influenza IM	Hepatitis B	Human papilloma	Herpes zoster
	Before initiating therapy
DMARD monotherapy	yes	yes	yes	yes	yes
Combination DMARDs	yes	yes	yes	yes	yes
TNFi biologics	yes	yes	yes	yes	yes
Non-TNFi biologics	yes	yes	yes	yes	yes
	While on therapy
DMARD monotherapy	yes	yes	yes	yes	yes
Combination DMARDs	yes	yes	yes	yes	yes
TNFi biologics	Strongly recommended	Yes Strongly recommended	Yes Strongly recommended	yes	Not recommended
Non-TNFi biologics	Strongly recommended	Yes Strongly recommended	Yes Strongly recommended	yes	Not recommended

 

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In Conclusion:

The ACR/ EULAR RA treatment guidelines focus on individualized treatment. Not all patients require the same treatment. Like the previous guidelines, the use of early initiation of DMARDs has been encouraged. These guidelines provide only guidance for the treating physicians, the clinical, social, and economic conditions must be kept in mind prior to prescribing the novel biological agents.