Rheumatoid Arthritis: Drug Therapy

Therapy goals

  • Remission (temporary or permanent remission of disease symptoms) of rheumatoid arthritis (RA).
  • Prevention or slowing of the destruction (“destruction”) of the affected joints.

Therapy recommendations

  • The overriding principle of therapy is that decisions are made together with the patient (shared decision).
  • Therapy escalation if the therapy goal is not achieved only after 3 months!
  • 1st therapy step:
    • In active (RA), basic therapy is started with methotrexate (MTX) as the first DMARD (disease modifying antirheumatic drugs).
    • Glucocorticoids (GC) should initially be administered in low to medium-high doses as a supplement to the DMARD, which should be phased out quickly, i.e. after 6 months! If necessary, also intraarticular (“into the joint cavity”) and peritendinous (“around the tendon”) injections of glucocorticosteroids.With the combination of MTX with GC can be achieved in up to 70% of cases, if started in time, a remission (temporary or permanent subsidence of disease symptoms).
  • In cases of moderate disease activity without unfavorable prognostic factors (e.g., marked inflammatory activity, highly positive rheumatology, and early onset of erosions) despite optimal monotherapy, secondary therapy is with a DMARD combination:
  • 2nd therapeutic step:
    • Lack of response to therapy after 12 weeks: DMARD therapy is supplemented by combination partners (see above under recommendations for “moderate disease activity without unfavorable prognostic factors”
  • 3rd therapeutic step:
    • Biologicals (biologics therapy) [see below].
      • If improvement still does not occur under this (after 3-6 months of therapy), MTX should be combined with biologicals (biologics therapy). Note: Infection prophylaxis must be performed before biologics therapy!
      • After insufficient response to two classical DMARDs (in combination), biologicals are recommended.
      • For the start with biologicals are no longer only the tumor necrosis factor (TNF) alpha inhibitor (anti TNF) but also equally the interleukin antagonists, etc. to choose from.
      • If the biologics therapy is not effective after 12 weeks, a change of strategy must be made.
  • Therapy phase-out/structured therapy de-escalation strategy: the prerequisite is a six- to twelve-month stable remission. First, the glucocorticoids should be phased out, then (for cost reasons) the biologicals (biologics) and finally the DMARD.
  • Pharmacotherapy of the elderly patient: Positive and negative recommendations (see below).
  • See also under “Further Therapy.”

A distinction is made between different groups of active substances:

  • Disease modifying antirheumatic drugs (DMARDs); here: conventional synthetic DMARDs:
    • Chelating agent (D-penicillamine* ).
    • Chloroquine
    • Gold*
    • Immunosuppressants (leflunomide, methotrexate (MTX))
    • Sulfonamides (sulfasalazine)
  • Immunosuppressants (drugs that reduce the functions of the immune system).
  • Glucocorticoids
    • Cushing’s threshold dose: 7.5 mg/dDaily dose of ≤ 5 mg prednisone equivalent carries an acceptably low risk; a daily dose of ≥ 10 mg increases the risk of harmful side effects
    • Short-term GC administration at initiation of 30 mg prednisolone per day (DGRh guideline) and switching therapy with conventional synthetic DMARDs (Disease Modifying Anti-Rheumatic Drugs; csDMARD).
    • Initial: short-term high dose that is rapidly reduced to the low-dose range (1-3 mg prednisolone 7d) (within eight weeks)
    • Duration of therapy no longer than 3-6 months
    • If necessary, also intraarticular and peritendinous injections of glucocorticosteroids.
  • Non-steroidal anti-inflammatory drugs (NSAIDs), e.g. dicofenac, indometacin, ibuprofen.
  • Biologicals (biologics; drugs produced by means of biotechnology) or biological DMARD (bDMARD).

* Should no longer be used due to the unfavorable spectrum of side effects! Glucocorticoids

  • Mode of action Glucocorticoids: anti-inflammatory (anti-inflammatory), immunosuppressive, anti-allergic, antiphlogistic (anti-inflammatory), antiproliferative (growth inhibitory).
  • Side effects: catabolic, diabetogenic (hyperglycemia/hyperglycemia), sodium retention (hypertension), increased liver enzyme levels, tendency to infection, wound healing disorder, ulcer tendency (tendency to ulceration).
  • Notice: In the SEMIRA study, all patients were treated with glucocorticoids for at least 6 months. In the control group, treatment was continued at a low prednisone dose for 6 months, whereas in the discontinuation regimen, therapy was gradually reduced and finally discontinued altogether after 4 months. Adjunctive therapy consisted of the interleukin-6 receptor antibody tocilizumab. Result: 77 percent of patients receiving a constant dose of prednisone succeeded in preventing re-inflammation (recurrence of inflammation); in the discontinuation group, the treatment success rate was 65%.

Biological

Active ingredient groups Active ingredients Special features
TNF-alpha inhibitors (anti-TNF) Adalimumab No studies on dose adjustmentMonotherapy possibleCave! Meningoencephalitis due to Epstein-Barr virus (EBV) after therapy with adalimumab (single case) [
Certolizumab pegol Possible if response to baseline therapy is inadequateMonotherapy.
Etanercept No dose adjustment necessaryMonotherapy possible.

See below UAW database

Golimumab If response to baseline therapy is inadequateNo monotherapy.
Infliximab Administration with methotrexateNo dose adjustment studiesNo monotherapy.
Interleukin-1 antagonists(IL-1 anatogonists). Anakinra Administration with methotrexateNo dose adjustment needed.
Interleukin-6 antagonists(IL-6 anatgonists). Tocilizumab (TCZ) Possible if response to baseline therapy is inadequateMonotherapy.

See below Red Hand Letter

T-cell costimulator inhibitor Abatacept If response to baseline therapy is inadequateNo monotherapy.
Anti-CD20 antibody Rituximab(RTX) If response to baseline therapy is inadequateNo monotherapy.
Janus kinase inhibitors

(JAK inhibitors)

Baricitinib Indication: moderate-to-severe RA patients in whom DMARDs have had no or inadequate effect.
Tofacitinib Indication: adult patients with moderate-to-severe active rheumatoid arthritis.

Note: Tofacitinib resulted in partially fatal pulmonary emboli in patients with rheumatoid arthritis (RA), at an increased dose ( 10 mg twice daily; recommended dose: 5 mg twice daily), which is not approved in patients with rheumatoid arthritis (RA).The PRAC* recommends that tofacitinib be used with caution in patients at increased risk for thrombosis. May also be given as monotherapy if intolerant to methotrexate or if treatment with methotrexate is not indicated.

* The Pharmacovigilance Risk Assessment Committee ( PRAC ) is the committee of the European Medicines Agency.Further references.

  • Tofacitinib: cases of serious drug-induced liver injury, including acute liver failure, hepatitis, and jaundice, which in some cases required liver transplantation.Liver monitoring: ALT (GPT) and AST (GOT): checked every four to eight weeks for the first six months of treatment and every 12 weeks thereafter. When considering treatment in patients with ALT or AST levels above 1.5 times normal, caution should be exercised. Treatment is not recommended for ALT or AST levels above 5 times normal.

Phytotherapeutics

  • Extracts of Tripterygium wilfordii Hook F (TwHF), which is recommended by traditional Chinese medicine (TCM) as a remedy for joint pain, fever, edema, and local inflammation, performed as well as the standard agent methotrexate in a randomized trial

Pharmacotherapy of the elderly patient: Positive and negative recommendations

  • Positive recommendations
    • Use of assessments proven in geriatrics on ability domains such as independence, mobility, cognition, and emotion.
    • Initiating a medication plan to promote medication therapy safety (AMTS) with continuous adjustment throughout the course.
    • The cardiovascular risk profile of patients with rheumatic diseases should be determined and reduced if necessary.
    • To consider the RABBIT score to assess the risk of infection associated with biologic administration.
    • More frequent use of biologics to reduce disease activity and comorbidities in elderly RA patients.
  • Negative recommendations
    • Prolonged glucocorticoid therapy at a dose of >5 mg/day prednisolone equivalent should not be undertaken.
    • MTX therapy should not be given without regular follow-up of renal function parameters.
    • The new prescription of a drug should not be made without review of the existing medication.
    • Oral osteoporosis therapy should be replaced with a parenteral form of administration in geriatric RA patients in the presence of ability impairment as well as geriatric-related mobility impairment (including instability and immobility).
    • Taking out sulfonylureas in type 2 diabetes of the elderly patient.

Supplements (dietary supplements; vital substances)

Suitable dietary supplements should contain the following vital substances:

Among other things, these lead to relief of pain and reduction of joint stiffness. Other dietary measures: Strong reduction in the intake of arachidonic acid from conventional food (see food list – arachidonic acid).