Ankylosing spondylitis medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview[edit | edit source]

Pharmacologic medical therapies for ankylosing spondylitis(AS) include Nonsteroidal anti-inflammatory drugs (NSAIDs), tumor necrosis factor (TNF) blocker, and interleukin 17 (IL-17) inhibitors.Ankylosing spondylitis (AS) is a chronic inflammatory disease which is manifested by back pain and gradually to spinal stiffness.While treating the AS patients the primary goal is to maximize long-term health-related quality of life.

Medical Therapy[edit | edit source]

• Medical therapy for AS is according to the guidelines proposed by ^[1][2][3]
  • Assessment of SpondyloArthritis international Society (ASAS)
  • European League Against Rheumatism (EULAR)
  • American College of Rheumatology (ACR)/Spondylitis Association of America (SAA)/Spondyloarthritis Research and Treatment Network (SPARTAN) collaboration 
• Pharmacologic medical therapies for ankylosing spondylitis(AS) include Nonsteroidal anti-inflammatory drugs (NSAIDs), tumor necrosis factor (TNF) blocker, analgesics, sulfasalazine,intraarticular injections and interleukin 17 (IL-17) inhibitors.

Nonsteroidal antiinflammatory drugs(NSAIDs)^{[4][5][6][7][8][9]}[edit | edit source]

• The first line treatment for all the patients who are having symptomatic ankylosing spondylitis (AS) are with Nonsteroidal antiinflammatory drugs(NSAIDs).
• 70 to 80 percent patients who are taking NSAIDs report substantial relief of back pain and stiffness.
• Play a crucial role in delaying the progression of ankylosing spondylitis.
• Regardless of which NSAID used, the maximum dose is usually required to manage AS.
• Treating with NSAIDs in AS especially in patients with increased erythrocyte sedimentation rate (ESR) shows especially effective in decreasing the ESR.^[10]

Adult

• Preferred regimen (1): Indomethacin: Initial: 75 mg once daily, may increase to 75 mg twice daily (maximum dose: 150 mg/day) for at least 4 weeks.^[11]
• Preferred regimen (2): Celecoxib or Etoricoxib: Oral: 200 mg once daily or 100 mg twice daily.^{[12][13][14][15][16][17]}

Tumor necrosis factor alpha antagonists(TNF-alpha)^{[18][19][20][21][22]}[edit | edit source]

• Infliximab, etanercept, adalimumab, certolizumab, and golimumab are the available tumor necrosis factor alpha inhibitors(TNF-alpha) to treat AS.
• In AS there is no much of a use in adding immunomodulatory drug, such as methotrexate (MTX) as the evidence shows no additional benefit but may increase the cost and the risk of adverse effects.^[23][24]
• Treating patients in AS with tumor necrosis factor alpha inhibitors(TNF-alpha) shows significant improvements in disease progress and function such as at least 40 percent improvement from baseline were seen.^[25]
• Adalimumab, etanercept, and infliximab have the same efficacy and potency in treating the AS patients.^[26]
• Patients who are getting treated with tumor necrosis factor alpha inhibitors shows approximately 80% good response and at least 50% improvement from the baseline of the disease.^[27]
• Response to TNF antagonists: The following parameters are sighs of a good response to TNF antagonists^[28][29]
  • Age, especially young patients.
  • Elevated C-reactive protein (CRP).
  • The best predictor is, Shorter disease duration.
• Treating with TNF alpha inhibitors in patients with AS shows beneficial effect in improving bone density.^[30][31][32]

Side Effects^[33][edit | edit source]

• Using TNF-alpha inhibitors increases the risk of reactivation of latent tuberculosis and
• Using TNF-alpha inhibitors increases the risk of exacerbation or development of demyelinating disease.

Adult Dosage

• Preferred regimen (1): Infliximab 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 6 weeks thereafter.
• Preferred regimen (2): Etanercept once-weekly dosing: 50 mg once weekly; maximum dose (rheumatoid arthritis): 50 mg/week.
• Preferred regimen (3): Adalimumab IV: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter.
• Preferred regimen (4): Certolizumab Initial: 400 mg, repeat dose 2 and 4 weeks after initial dose; Maintenance: 200 mg every 2 weeks or 400 mg every 4 weeks.

Disease-modifying antirheumatic drugs(DMARDs)[edit | edit source]

• The use of DMARDs regarded as useful but is limited in AS patients with sulfasalazine.
  • Preferred regimen (1): Oral: Initial: 500 mg once daily; may increase up to 2 to 3 g/day in divided doses.

Other DMARDs

• Methotrexate

• Leflunomide

Glucocorticoids[edit | edit source]

• Pharmacologic medical therapies for Ankylosing spondylitis (AS) include Glucocorticoids but using them for long term basis for patients is not suggested, although high doses of prednisolone may have shown some benefit for very short-term therapy.^[34]

• Prednisolone has dose-dependent therapeutic properties in AS.^[35][36]
  • Preferred regimen (1): Prednisolone: oral: 0.1 to 2 mg/kg/day in 3 or 4 divided dose.

Monoclonal antibody^[37][38][edit | edit source]

• In the United States Secukinumab has been approved for use in patients with AS.^[39]
• Secukinumab, is an anti-interleukin (IL)-17A monoclonal antibody.^[40]
• IL-17A a proinflammatory cytokine which plays important role in the pathogenesis of AS.^[41]
  • Preferred regimen (1): Secukinumab:150 mg administered subcutaneously weekly for four weeks, then every four weeks thereafter.
  • Preferred regimen (2): Ustekinumab: IV: Infuse over at least 1 hour; use of IV set with an in-line, low-protein binding filter (0.2 micrometer) required.
  • Preferred regimen (3): Pamidronate:30 mg/10 mL (10 mL); 90 mg/10 mL (10 mL).^[42] 
  • Preferred regimen (4): Rituximab  IV: 1,000 mg on days 1 and 15.^[43]

Turmeric^[44][45][edit | edit source]

• Curcuma longa (turmeric) has a very long history of extensive use in Ayurvedic medicine as a treatment for inflammatory conditions in India.^[46]
• Turmeric contains 3 active components called curcuminoids^[47]
  • Curcumin(diferuloylmethane)
  • Demethoxycurcumin
  • Bisdemethoxycurcumin

• Turmeric when administered orally in the diet improves both the wasting and histopathological signs of inflammation.
• Curcumin also suppress the expression of inflammatory cytokines such as TNF-α.
• Curcumin when combined with IL-10, curcumin inhibited NF-κB quite effectively.^[48]
  • Preferred regimen(1): Turmeric :150 mg of curcumin twice daily, decreases the levels of expression of inflammatory cytokines such as TNF-α and IL-6 in serum.^[49]
  • Preferred regimen(2):Turmeric: 2 gms/day of curcumin can suppress NF-κB activation.^[50]

References[edit | edit source]

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