Last updated December 15, 2022

Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

Treatment

Recommendations for the Treatment of Adults With AS (Table 2)

1. We strongly recommend treatment with NSAIDs over no treatment with NSAIDsa. ( Moderate , )
608
2. We conditionally recommend continuous treatment with NSAIDs over on-demand treatment with NSAIDs. ( Moderate , )
608
3. We do not recommend any particular NSAID as the preferred choice.a ( Moderate , )
608
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. (Low to moderate, )
608
5. In adults with active AS despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with tofacitinib. (Very low-quality evidence)
608
6. In adults with active AS despite treatment with NSAIDs, we strongly recommend treatment with TNFi over no treatment with TNFi. (High-quality evidence)
608
7. We do not recommend any particular TNFi as the preferred choice. (Moderate to high, )
608
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 , )
608
9. In adults with active AS despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with secukinumab or ixekizumab. (Low to moderate, )
608
10. In adults with active AS despite treatment with NSAIDs, we conditionally recommend treatment with secukinumab or ixekizumab over treatment with tofacitinib. (Very low-quality evidence)
608
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. ( Moderate , )
608
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. (Low to moderate, )
608
13. In adults with active AS despite treatment with the first TNFi used, we conditionally recommend treatment with a different TNFi biologic in patients with secondary nonresponse to TNFi. (Low to moderate, )
608
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. (Low to moderate, )
608
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. (Low to moderate, )
608
16. We strongly recommend against treatment with systemic glucocorticoids.a (Low to moderate, )
608
17. In adults with isolated active sacroiliitis despite treatment with NSAIDsa, we conditionally recommend treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids. (Low to moderate, )
608
18. In adults with stable axial disease and active enthesitis despite treatment with NSAIDsa, 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. (Low to moderate, )
608
19. In adults with stable axial disease and active peripheral arthritis despite treatment with NSAIDsa, we conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids. (Low to moderate, )
608
20. We strongly recommend treatment with physical therapy over no treatment with physical therapy.a (Moderate to high, )
608
21. We conditionally recommend active physical therapy interventions (supervised exercise) over passive physical therapy interventions (massage, ultrasound, heat).a (Low to moderate, )
608
22. We conditionally recommend land-based physical therapy interventions over aquatic therapy interventions.a (Moderate to high, )
608

Recommendations for Adults With Stable AS

23. We conditionally recommend on-demand treatment with NSAIDs over continuous treatment with NSAIDs. (Low-quality evidence)
608
24. In adults receiving treatment with TNFi and NSAIDs, we conditionally recommend continuing treatment with TNFi alone compared to continuing both treatments. (Low to moderate, )
608
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. (Low to moderate, )
608
26. In adults receiving treatment with a biologic, we conditionally recommend against discontinuation of the biologic. (Low to moderate, )
608
27. In adults receiving treatment with a biologic, we conditionally recommend against tapering of the biologic dose as a standard approach. (Low to moderate, )
608
28. In adults receiving treatment with an originator TNFi, we strongly recommend continuing treatment with the originator TNFi over mandated switching to its biosimilar. (Low to moderate, )
608
29. We strongly recommend treatment with physical therapy over no treatment with physical therapy.a ( Moderate , )
608

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. ( Moderate , )
608
31. We conditionally recommend advising unsupervised back exercises.a (Moderate to high, )
608
32. We conditionally recommend fall evaluation and counseling.a (Low to moderate, )
608
33. We conditionally recommend participation in formal group or individual self-management education.a (Moderate to high, )
608
34. In adults with spinal fusion or advanced spinal osteoporosis, we strongly recommend against treatment with spinal manipulation.a (Low to moderate, )
608
35. In adults with advanced hip arthritis, we strongly recommend treatment with total hip arthroplasty over no surgery.a (Low to moderate, )
608
36. In adults with severe kyphosis, we conditionally recommend against elective spinal osteotomy.a (Low to moderate, )
608

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 (Low to moderate, )
608
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 (Low to moderate, )
608
39. In adults with recurrent iritis, we conditionally recommend treatment with TNFi monoclonal antibodies over treatment with other biologics. (Low-quality evidence)
608
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 (Low to moderate, )
608
41. In adults with inflammatory bowel disease, we conditionally recommend treatment with TNFi monoclonal antibodies over treatment with other biologics. (Low to moderate, )
608

Disease Activity Assessment, Imaging, and Screening

42. We conditionally recommend the regular-interval use and monitoring of a validated ASa disease activity measure. (Low to moderate, )
608
43. We conditionally recommend regular-interval use and monitoring of CRP concentrations or ESR over usual care without regular CRP or ESRa monitoring. (Low to moderate, )
608
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. ( Moderate , )
608
45. We conditionally recommend screening for osteopenia/osteoporosis with DXA scan over no screening.a (Low to moderate, )
608
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 (Low to moderate, )
608
47. We strongly recommend against screening for cardiac conduction defects with electrocardiograms.a (Low to moderate, )
608
48. We strongly recommend against screening for valvular heart disease with echocardiograms.a (Low to moderate, )
608
49. In adults with AS of unclear activity while on a biologic, we conditionally recommend obtaining a spinal or pelvis MRI to assess activity. (Low to moderate, )
608
50. In adults with stable AS, we conditionally recommend against obtaining a spinal or pelvis MRI to confirm inactivity. (Low to moderate, )
608
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. (Low to moderate, )
608
a These recommendations were from 2015 and were not reviewed in this update. The number preceding the recommendation is the recommendation number and is referenced as bracketed numbers in Figure 1.

Recommendations for the Treatment of Adults With Nonradiographic Axial SpA (Table 3)

Recommendations for Adults With Active Nonradiographic Axial SpA

52. We strongly recommend treatment with NSAIDs over no treatment with NSAIDsa. (Low to moderate, )
608
53. We conditionally recommend continuous treatment with NSAIDs over on-demand treatment with NSAIDs. (Low to moderate, )
608
54. We do not recommend any particular NSAID as the preferred choice.a (Low to moderate, )
608
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-quality evidence)
608
56. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we strongly recommend treatment with TNFi over no treatment with TNFi. ( High , )
608
57. We do not recommend any particular TNFi as the preferred choice. (Low to moderate, )
608
58. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with tofacitinib. (Low to moderate, )
608
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. (Low to moderate, )
608
60. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi over treatment with secukinumab or ixekizumab. (Low to moderate, )
608
61. In adults with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with secukinumab or ixekizumab over treatment with tofacitinib. (Low to moderate, )
608
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. (Low to moderate, )
608
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. (Low to moderate, )
608
64. In adults with active nonradiographic axial SpA and secondary nonresponse to the first TNFi used, we conditionally recommend switching to a different TNFi and secondary nonresponse to the first TNFi used, we conditionally recommend switching to a different TNFi over switching to a non-TNFi biologic. (Low to moderate, )
608
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. (Low to moderate, )
608
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. (Low to moderate, )
608
67. We strongly recommend against treatment with systemic glucocorticoids.a (Low to moderate, )
608
68. In adults with isolated active sacroiliitis despite treatment with NSAIDsa, we conditionally recommend treatment with local glucocorticoids over no treatment with local glucocorticoids. (Very low-quality evidence)
608
69. In adults with active enthesitis despite treatment with NSAIDsa, 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. (Low to moderate, )
608
70. In adults with active peripheral arthritis despite treatment with NSAIDsa, we conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids. (Low to moderate, )
608
71. We strongly recommend treatment with physical therapy over no treatment with physical therapy.a ( Moderate , )
608
72. We conditionally recommend active physical therapy interventions (supervised exercise) over passive physical therapy interventions (massage, ultrasound, heat).a (Low to moderate, )
608
73. We conditionally recommend land-based physical therapy interventions over aquatic therapy interventions.a (Low to moderate, )
608

Recommendations for Adults With Stable Nonradiographic Axial SpA

74. We conditionally recommend on-demand treatment with NSAIDs over continuous treatment with NSAIDs. (Very low-quality evidence)
608
75. In adults receiving treatment with TNFi and NSAIDs, we conditionally recommend continuing treatment with TNFi alone compared to continuing both medications. (Low to moderate, )
608
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. (Low to moderate, )
608
77. In adults receiving treatment with a biologic, we conditionally recommend against discontinuation of the biologic. ( Moderate , )
608
78. In adults receiving treatment with a biologic, we conditionally recommend against tapering of the biologic dose as a standard approach. (Low to moderate, )
608
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. (Low to moderate, )
608

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. ( Moderate , )
608

Disease Activity Assessment and Imaging

81. We conditionally recommend the regular-interval use and monitoring of a validated ASa disease activity measure. (Low to moderate, )
608
82. We conditionally recommend regular-interval use and monitoring of the CRP concentrations or ESR over usual care without regular CRP or ESRa monitoring. (Low to moderate, )
608
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. (Low to moderate, )
608
84. In adults with nonradiographic axial SpA of unclear activity while on a biologic, we conditionally recommend obtaining a pelvis MRI to assess activity. (Low to moderate, )
608
85. In adults with stable nonradiographic axial SpA, we conditionally recommend against obtaining a spinal or pelvis MRI to confirm inactivity. (Low to moderate, )
608
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. (Low to moderate, )
608
a These recommendations were from 2015 and were not reviewed in this update. The number preceding the recommendation is the recommendation number and is referenced as bracketed numbers in Figure 1.

Recommendation Grading

Overview

Title

Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

Authoring Organizations

Publication Month/Year

August 22, 2019

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Counseling, Management, Treatment

Diseases/Conditions (MeSH)

D013167 - Spondylitis, Ankylosing, D025241 - Spondylarthritis

Keywords

ankylosing spondylitis, axial spondyloarthritis

Source Citation

 

Ward, M.M., Deodhar, A., Gensler, L.S., Dubreuil, M., Yu, D., Khan, M.A., Haroon, N., Borenstein, D., Wang, R., Biehl, A., Fang, M.A., Louie, G., Majithia, V., Ng, B., Bigham, R., Pianin, M., Shah, A.A., Sullivan, N., Turgunbaev, M., Oristaglio, J., Turner, A., Maksymowych, W.P. and Caplan, L. (2019), 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Care Res, 71: 1285-1299. doi:10.1002/acr.24025

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
183
Literature Search Start Date
January 1, 1966
Literature Search End Date
February 28, 2018
Description of External Review Process
Principal Investigators (PIs) are asked to share a draft of the near-final guideline paper with the ACR Guideline Subcommittee chair and staff liaison to the guideline project development group before submission for journal or ACR approval. The subcommittee chair / staff liaison will examine the paper with organizational policies and high-level project goals in mind and provide any relevant feedback to the PI. The authors are required to respond to this feedback with related manuscript revisions; if PIs disagree with the feedback and do not wish to make requested revisions, they should discuss this with the subcommittee chair/staff liaison until consensus can be reached.
Description of Public Comment Process
The ACRh Clinical Methodology Manual describes the process for posting Clinical Guidelines for public comment on the society’s website. Feedback is evaluated prior to systematic review begins. Responses are included in the document. Public comments will be collected after publication.
Specialties Involved
Family Medicine, Geriatric Medicine, Internal Medicine General, Orthopaedic Surgery, Rheumatology
Description of Systematic Review
Use of GRADE to Evaluate the Evidence and Develop Recommendations Beginning in late 2011, the ACR will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology for all new guideline development projects, including systematic reviews of evidence and guideline recommendations. Information about GRADE may be found online at http://www.gradeworkinggroup.org/ , including a 20-part guide on GRADE from the Journal of Clinical Epidemiology.
List of Questions
The guideline addressed 24 PICO questions in four topic areas: pharmacological therapy, comorbidities, treatment strategies, and imaging. Parallel questions were developed on most topics for nr-axSpA, which expanded the total number of PICO questions to 46. Approximately one-half of the PICO questions were derived from the 2015 5 ACR/SAA/SPARTAN AS and nr-axSpA guidelines and one-half were developed de novo. The PICO questions were posted for 30 days on the ACR website for public comment and revised accordingly
Description of Study Criteria
A systematic literature review is used as the basis for development of the recommendations within all ACR guidelines. The systematic review is based on a project protocol (i.e., project plan) that is developed by the project PI, systematic review team leader, and the rest of the Core Team, as well as selected project participants (including the systematic review team and the leader of the guideline panel, if the project PI is not also serving in this role), in conjunction with the ACR. In addition to serving as the basis for the literature review, the protocol guides project leaders and participants as they work to accomplish the goals and objectives of the project. The protocol is essential to minimize bias[15] and to ensure that the end product(s) delivered meet the needs of the ACR membership and the original intent of the project. The protocol will address broad specifications for the project, as well as the detailed information related to the systematic review. (See below for more details of what will be included in the project protocol and Appendix 8 for the ACR protocol template.) Specific clinical questions need to be answered in the systematic review, and the literature search strategy is based on these questions. The “PICO” format informs the key questions/clinical questions being asked. The acronym PICO stands for Population (condition(s), patient, or problem being addressed); Interventions (e.g., treatment), Comparator (alternative intervention for comparison), and Outcomes (clinical outcomes of interest). Important and critical outcomes should be the focus, i.e., as defined by patient or clinician, rather than those driven by available evidence. In addition to PICO, pre-specified types of studies are included as part of the criteria for the systematic review development. Sometimes the setting is also an important aspect of the question. The systematic review leader and team, with input from the project PI and the guideline panel leader, develop PICO questions for each guideline project using a consensus process involving the Guideline Subcommittee, an adequately representative sample of clinicians, and the patient/consumer representative(s). Once the clinical questions have been developed, they are included in the project protocol for ACR approval and subsequent public comment via the online feedback mechanism described below.
Description of Search Strategy
The protocol will also include how studies will be identified (and include an electronic strategy for Medline/PubMed search with a notation that the search will be modified for other named databases, and how and if gray literature will be identified), inclusion and exclusion criteria for studies, information about quality assessment, and a priori specification, for example, about how to deal with such methodological issues as heterogeneity.
Description of Study Selection
A literature review leader is determined (unless done by third party). A literature review team of approximately 4-5 people will conduct the review of available evidence that will serve as the basis of the recommendations made in the guideline. At least 51% of the literature team must have no COI. Disagreements were resolved through consensus. Evidence tables are provided in the manuscript and/or in Data Supplement. ** The Literature Review Team (5 members plus a Literature Review Lead was comprised of two rheumatologists, two health services researchers, and two internists with special 2 expertise in the conduct of literature reviews. The Literature Review Team conducted a systematic search, screened papers for relevance, assessed study quality, extracted data, computed pooled estimates of outcomes, graded the quality of evidence, generated the Summary of Findings (SoF) tables, and compiled an evidence report.
Description of Evidence Analysis Methods
ACRh describes the overall methodology in the 2015 Clinical Methodology Manual. The details of the process used for this guideline are published in the supplements. The systematic review team compiles output from the systematic review to help inform the drafting of recommendations. This information takes the form of Evidence Profiles that provide simple, transparent summaries of the quality of evaluated studies and their findings relevant to the outcomes being examined in the guideline. The Summary of Findings information includes a qualification of the quality of evidence as very low, low, moderate or high, based on several factors explicitly outlined in the GRADE methodology.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect.
Description of Recommendation Grading
Once this work has been completed by the systematic review team, each guideline panel member is asked to consider the quality of available evidence, judge the balance between desirable and undesirable effects, consider patient / clinician values and preferences as well as resource allocation (i.e., cost), and determine what type and strength of recommendations should be made. The strength of the recommendations is categorized as either “strong” or “conditional.” Typically, if panel members are very certain that benefits do, or do not, outweigh risks and burdens, they will make a strong recommendation. If panel members decide that benefits and risks/burdens are balanced, and/or considerable uncertainty exists about the magnitude of benefits and risks, they may make a conditional recommendation. In addition, when panel members believe that fully informed patients are likely to make different choices based on their own values and preferences despite strong evidence, they will likely offer a conditional recommendation. The Voting Panel made strong recommendations when it inferred compelling evidence of efficacy and that benefits clearly outweighed harms and burdens. Thus, a strong recommendation means that the Voting Panel was confident that the desirable effects of following the recommendation outweigh potential undesirable effects (or vice versa), so the course of action would apply to all or almost all patients, and only a small proportion of patients would not want to follow the recommendation. The Voting Panel made conditional recommendations when the quality of the evidence proved low or very low and/or the balance of benefits versus harms and burdens was sufficiently close that shared decision-making between the patient and the clinician would be particularly important. Conditional recommendations are those for which the majority of informed patients would choose to follow the recommended course of action, but some would not. Thus, conditional recommendations are particularly value- and preference-sensitive and always warrant a full shared decision-making approach involving a complete and clear explication of benefits, harms, and burdens in language and in a context that patients understand.
Description of Funding Source
ACRh provides funding for Guideline Development.
Company/Author Disclosures
ACRh’s Conflict of Interest Policy is provided in the ACRh Clinical Guideline Methodology Manual. Disclosures of relationships are obtained from anyone contributing intellectually to an ACR guideline development project, using either the ACR or the journals’ disclosure forms, depending on the stage of the project/review. This disclosure happens at various points in the application, development and approval process, both in writing and verbally.
Percentage of Authors Reporting COI
100