Key Points
- Axial spondyloarthritis (SpA), comprising ankylosing spondylitis (AS) and nonradiographic axial SpA, is the main form of chronic inflammatory arthritis affecting the axial skeleton.
- AS affects 0.1–0.5% of the population and is characterized by inflammatory back pain, radiographic sacroiliitis, excess spinal bone formation, and a high prevalence of HLA–B27.
- The severity of arthralgia, stiffness, and limited flexibility varies widely among patients and over the course of axial SpA.
- Skeletal disease may be accompanied by uveitis, psoriasis, and inflammatory bowel disease (IBD).
- The goals of treatment are to alleviate symptoms, improve functioning, maintain the ability to work, decrease disease complications, and forestall skeletal damage as much as possible.
Table 1. Definitions of Key Terms
| Term | Definition |
|---|---|
| Active disease | Disease causing symptoms at an unacceptably bothersome level to the patient and judged by the examining clinician to be due to inflammation. |
| Stable disease | Disease that was asymptomatic or causing symptoms but at an acceptable level as reported by the patient. A minimum of 6 months was required to qualify as clinically stable. |
| Primary nonresponse | Absence of a clinically meaningful improvement in disease activity over the 3 to 6 months after treatment initiation, not related to toxicity or poor adherence. |
| Secondary nonresponse | Recurrence of ankylosing spondylitis activity, not due to treatment interruption or poor adherence, after having a sustained clinically meaningful improvement on treatment (generally, beyond the initial 6 months of treatment). |
| Conventional synthetic antirheumatic drug | Sulfasalazine, methotrexate, leflunomide, apremilast, thalidomide, pamidronate. |
| Biosimilar | Biopharmaceuticals that are copies of an original biologic medication and tested to be of the same purity and potency as the original. In these recommendations, we refer only to TNFi biosimilars. Examples include infliximab-dyyb, etanercept-szzs, and adalimumab-atto. |
| TNFi | Infliximab, etanercept, adalimumab, certolizumab, golimumab, and their biosimilars. |
| TNFi monoclonal antibodies | Infliximab, adalimumab, certolizumab, golimumab. |
| Biologics | TNFi, abatacept, rituximab, sarilumab, tocilizumab, ustekinumab, secukinumab, ixekizumab |
| Patient preferences | Beliefs and expectations regarding potential benefits and harms of treatment and how these relate to an individual’s goals for health and life. |
| Shared decision-making | The process by which a patient and clinician arrive at an individualized treatment decision based on an understanding of the potential benefits and risks of available treatment options and of a patient’s values and preferences. |
Treatment
Table 2. Recommendations for the Treatment of Adults With AS
| Recommendation | Level of Evidence |
|---|---|
| Recommendations For Adults With Active AS | |
| 1. We strongly recommend treatment with NSAIDs over no treatment with NSAIDs.a | Low |
| 2. We conditionally recommend continuous treatment with NSAIDs over on-demand treatment with NSAIDs. | Low to moderate |
| 3. We do not recommend any particular NSAID as the preferred choice.a | Low to moderate |
| 4. In adults with active AS despite treatment with NSAIDs, we conditionally recommend treatment with sulfasalazine, methotrexate, or tofacitinib over no treatment with these medications. Sulfasalazine or methotrexate should be considered only in patients with prominent peripheral arthritis or when TNFi are not available. | Very low to moderate |
| 5. In adults with active AS despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with tofacitinib. | Very low |
| 6. In adults with active AS despite treatment with NSAIDs, we strongly recommend treatment with TNFi over no treatment with TNFi. | High |
| 7. We do not recommend any particular TNFi as the preferred choice. | Moderate |
| 8. In adults with active AS despite treatment with NSAIDs, we strongly recommend treatment with secukinumab or ixekizumab over no treatment with secukinumab or ixekizumab. | High |
| 9. In adults with active AS despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with secukinumab or ixekizumab. | Very low |
| 10. In adults with active AS despite treatment with NSAIDs, we conditionally recommend treatment with secukinumab or ixekizumab over treatment with tofacitinib. | Very low |
| 11. In adults with active AS despite treatment with NSAIDs and who have contraindications to TNFi, we conditionally recommend treatment with secukinumab or ixekizumab over treatment with sulfasalazine, methotrexate, or tofacitinib. | Low |
| 12. In adults with active AS despite treatment with the first TNFi used, we conditionally recommend treatment with secukinumab or ixekizumab over treatment with a different TNFi in patients with primary nonresponse to TNFi. | Very low |
| 13. In adults with active AS despite treatment with the first TNFi used, we conditionally recommend treatment with a different TNFi over treatment with a non-TNFi biologic in patients with secondary nonresponse to TNFi. | Very low |
| 14. In adults with active AS despite treatment with the first TNFi used, we strongly recommend against switching to treatment with a biosimilar of the first TNFi. | Very low |
| 15. In adults with active AS despite treatment with the first TNFi used, we conditionally recommend against the addition of sulfasalazine or methotrexate in favor of treatment with a new biologic. | Very low |
| 16. We strongly recommend against treatment with systemic glucocorticoids.a | Very low |
| 17. In adults with isolated active sacroiliitis despite treatment with NSAIDs, we conditionally recommend treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids.a | Very low |
| 18. In adults with stable axial disease and active enthesitis despite treatment with NSAIDs, we conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids. Peri-tendon injections of Achilles, patellar, and quadriceps tendons should be avoided.a | Very low |
| 18. In adults with stable axial disease and active enthesitis despite treatment with NSAIDs, we conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids. Peri-tendon injections of Achilles, patellar, and quadriceps tendons should be avoided.a | Very low |
| 19. In adults with stable axial disease and active peripheral arthritis despite treatment with NSAIDs, we conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids.a | Very low |
| 20. We strongly recommend treatment with physical therapy over no treatment with physical therapy.a | Moderate |
| 21. We conditionally recommend active physical therapy interventions (supervised exercise) over passive physical therapy interventions (massage, ultrasound, heat).a | Very low |
| 22. We conditionally recommend land-based physical therapy interventions over aquatic therapy interventions.a | Moderate |
| Recommendations for Adults With Stable AS | |
| 23. We conditionally recommend on-demand treatment with NSAIDs over continuous treatment with NSAIDs. | Low to moderate |
| 24. In adults receiving treatment with TNFi and NSAIDs, we conditionally recommend continuing treatment with TNFi alone compared to continuing both treatments. | Very low |
| 25. In adults receiving treatment with TNFi and a conventional synthetic antirheumatic drug, we conditionally recommend continuing treatment with TNFi alone over continuing both treatments. | Very low |
| 26. In adults receiving treatment with a biologic, we conditionally recommend against discontinuation of the biologic. | Very low to low |
| 27. In adults receiving treatment with a biologic, we conditionally recommend against tapering of the biologic dose as a standard approach. | Very low to low |
| 28. In adults receiving treatment with an originator TNFi, we strongly recommend continuing treatment with the originator TNFi over mandated switching to its biosimilar. | Very low |
| 29. We strongly recommend treatment with physical therapy over no treatment with physical therapy.a | Low |
| Recommendations for Adults With Active or Stable AS | |
| 30. In adults receiving treatment with TNFi, we conditionally recommend against co-treatment with low-dose methotrexate. | Low |
| 31. We conditionally recommend advising unsupervised back exercises.a | Moderate |
| 32. We conditionally recommend fall evaluation and counseling.a | Very low |
| 33. We conditionally recommend participation in formal group or individual self-management education.a | Moderate |
| 34. In adults with spinal fusion or advanced spinal osteoporosis, we strongly recommend against treatment with spinal manipulation.a | Very low |
| 35. In adults with advanced hip arthritis, we strongly recommend treatment with total hip arthroplasty over no surgery.a | Very low |
| 36. In adults with severe kyphosis, we conditionally recommend against elective spinal osteotomy.a | Very low |
| Recommendations for Adults With AS-Related Comorbidities | |
| 37. In adults with acute iritis, we strongly recommend treatment by an ophthalmologist to decrease the severity, duration, or complications of episodes.a | Very low |
| 38. In adults with recurrent iritis, we conditionally recommend prescription of topical glucocorticoids over no prescription for prompt at-home use in the event of eye symptoms to decrease the severity or duration of iritis episodes.a | Very low |
| 39. In adults with recurrent iritis, we conditionally recommend treatment with TNFi monoclonal antibodies over treatment with other biologics. | Low |
| 40. In adults with inflammatory bowel disease, we do not recommend any particular NSAID as the preferred choice to decrease the risk of worsening of inflammatory bowel disease symptoms.a | Very low |
| 41. In adults with inflammatory bowel disease, we conditionally recommend treatment with TNFi monoclonal antibodies over treatment with other biologics. | Very low |
| Disease Activity Assessment, Imaging, and Screening | |
| 42. We conditionally recommend the regular-interval use and monitoring of a validated AS disease activity measure.a | Very low |
| 43. We conditionally recommend regular-interval use and monitoring of CRP concentrations or ESR over usual care without regular CRP or ESR monitoring.a | Very low |
| 44. In adults with active AS, we conditionally recommend against using a treat-to-target strategy using a target of ASDAS <1.3 (or 2.1) over a treatment strategy based on physician assessment. | Low |
| 45. We conditionally recommend screening for osteopenia/osteoporosis with DXA scan over no screening.a | Very low |
| 46. In adults with syndesmophytes or spinal fusion, we conditionally recommend screening for osteoporosis/osteopenia with DXA scan of the spine as well as the hips, compared to DXA scan solely of the hip or other non-spine sites.a | Very low |
| 47. We strongly recommend against screening for cardiac conduction defects with electrocardiograms.a | Very low |
| 48. We strongly recommend against screening for valvular heart disease with echocardiograms.a | Very low |
| 49. In adults with AS of unclear activity while on a biologic, we conditionally recommend obtaining a spinal or pelvis MRI to assess activity. | Very low |
| 50. In adults with stable AS, we conditionally recommend against obtaining a spinal or pelvis MRI to confirm inactivity. | Very low |
| 51. In adults with active or stable AS on any treatment, we conditionally recommend against obtaining repeat spine radiographs at a scheduled interval (e.g., every 2 years) as a standard approach. | Very low |
Table 3. Recommendations for the Treatment of Adults With Nonradiographic Axial SpA
| Recommendation | Level of Evidence |
|---|---|
| Recommendations for Adults With Active Nonradiographic Axial SpA | |
| 52. We strongly recommend treatment with NSAIDs over no treatment with NSAIDs.a | Very low |
| 53. We conditionally recommend continuous treatment with NSAIDs over on-demand treatment with NSAIDs. | Very low |
| 54. We do not recommend any particular NSAID as the preferred choice.a | Very low |
| 55. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with sulfasalazine, methotrexate, or tofacitinib over no treatment with these medications. | Very low |
| 56. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we strongly recommend treatment with TNFi over no treatment with TNFi. | High |
| 57. We do not recommend any particular TNFi as the preferred choice. | Very low |
| 58. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with tofacitinib. | Very low |
| 59. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with secukinumab or ixekizumab over no treatment with secukinumab or ixekizumab. | Very low |
| 60. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with secukinumab or ixekizumab. | Very low |
| 61. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with secukinumab or ixekizumab over treatment with tofacitinib. | Very low |
| 62. In adults with active nonradiographic axial SpA despite treatment with NSAIDs and who have contraindications to TNFi, we conditionally recommend treatment with secukinumab or ixekizumab over treatment with sulfasalazine, methotrexate, or tofacitinib. | Very low |
| 63. In adults with active nonradiographic axial SpA and primary nonresponse to the first TNFi used, we conditionally recommend switching to secukinumab or ixekizumab over switching to a different TNFi. | Very low |
| 64. In adults with active nonradiographic axial SpA and secondary nonresponse to the first TNFi used, we conditionally recommend switching to a different TNFi over switching to a non-TNFi biologic. | Very low |
| 65. In adults with active nonradiographic axial SpA despite treatment with the first TNFi used, we strongly recommend against switching to the biosimilar of the first TNFi. | Very low |
| 66. In adults with active nonradiographic axial SpA despite treatment with the first TNFi used, we conditionally recommend against the addition of sulfasalazine or methotrexate in favor of treatment with a different biologic. | Very low |
| 67. We strongly recommend against treatment with systemic glucocorticoids.a | Very low |
| 68. In adults with isolated active sacroiliitis despite treatment with NSAIDs, we conditionally recommend treatment with local glucocorticoids over no treatment with local glucocorticoids.a | Very low |
| 69. In adults with active enthesitis despite treatment with NSAIDs, we conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids. Peri-tendon injections of Achilles, patellar, and quadriceps tendons should be avoided.a | Very low |
| 70. In adults with active peripheral arthritis despite treatment with NSAIDs, we conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids.a | Very low |
| 71. We strongly recommend treatment with physical therapy over no treatment with physical therapy.a | Low |
| 72. We conditionally recommend active physical therapy interventions (supervised exercise) over passive physical therapy interventions (massage, ultrasound, heat).a | Very low |
| 73. We conditionally recommend land-based physical therapy interventions over aquatic therapy interventions.a | Very low |
| Recommendations for Adults With Stable Nonradiographic Axial SpA | |
| 74. We conditionally recommend on-demand treatment with NSAIDs over continuous treatment with NSAIDs. | Very low |
| 75. In adults receiving treatment with TNFi and NSAIDs, we conditionally recommend continuing treatment with TNFi alone compared to continuing both medications. | Very low |
| 76. In adults receiving treatment with TNFi and a conventional synthetic antirheumatic drug, we conditionally recommend continuing treatment with TNFi alone over continuing treatment with both medications. | Very low |
| 77. In adults receiving treatment with a biologic, we conditionally recommend against discontinuation of the biologic. | Low |
| 78. In adults receiving treatment with a biologic, we conditionally recommend against tapering of the biologic dose as a standard approach. | Very low |
| 79. In adults receiving treatment with an originator TNFi, we strongly recommend continuation of treatment with the originator TNFi over mandated switching to its biosimilar. | Very low |
| Recommendations for Adults With Active or Stable Nonradiographic Axial SpA | |
| 80. In adults receiving treatment with TNFi, we conditionally recommend against co-treatment with low-dose methotrexate. | Low |
| Disease Activity Assessment and Imaging | |
| 81. We conditionally recommend the regular-interval use and monitoring of a validated AS disease activity measure.a | Very low |
| 82. We conditionally recommend regular-interval use and monitoring of the CRP concentrations or ESR over usual care without regular CRP or ESR monitoring.a | Very low |
| 83. In adults with active nonradiographic axial SpA, we conditionally recommend against using a treat-to-target strategy using a target of ASDAS <1.3 (or 2.1) over a treatment strategy based on physician assessment. | Very low |
| 84. In adults with nonradiographic axial SpA of unclear activity while on a biologic, we conditionally recommend obtaining a pelvis MRI to assess activity. | Very low |
| 85. In adults with stable nonradiographic axial SpA, we conditionally recommend against obtaining a spinal or pelvis MRI to confirm inactivity. | Very low |
| 86. In adults with active or stable nonradiographic axial SpA on any treatment, we conditionally recommend against obtaining repeat spine radiographs at a scheduled interval (e.g., every 2 years) as a standard approach. | Very low |
Figure 1A. Treatment of Patients With Active AS
Figure 1B. Treatment of Patients With Stable AS
