<p>Supplemental Table 4. Literature identified on treatment efficacy in nr-axSpA versus AS</p><p>Primary Study AS nr-axSpA Relevant findings author design patients patients </p><p>(reference) (n) (n) Treatment efficacy, n = 14 Callhoff (42) Meta- NR NR  Lower effect sizes of TNFα blockers on </p><p> analysis BASDAI and BASFI in nr-axSpA patients Ciurea (17) OBS 565 161  Response rate (BASDAI50, ASDAS CII, </p><p>ASDAS MI, ASDAS ID, ASAS-PR) to TNFα </p><p> inhibitors not significantly higher in AS </p><p> patients </p><p> ASAS40 significantly higher in AS patients Corli (53) OBS 263 98  Treatment response, drug survival, and </p><p> patient outcomes after initiation of first-</p><p> line TNFα inhibitor similar </p><p> BASDAI20 and BASDAI50 of TNFα inhibitors</p><p> at 12 months not significantly different Landewé (31) RCT 178 147  ASAS20, ASAS40, and ASDAS after </p><p> treatment with certolizumab pegol similar Lubrano (57) OBS 259 62  Probability of obtaining partial remission </p><p> during treatment with TNFα inhibitors not </p><p> significantly different</p><p> Partial remission significantly associated </p><p> with the absence of peripheral arthritis, </p><p> enthesitis, and psoriasis at baseline in </p><p> patients with AS, but not nr-axSpA Moltó (68) OBS 127 72  ASAS40 significantly correlated with sacroiliitis on MRI Poddubnyy RCT 17 17  Sustained and similar clinical response </p><p>(69) (ASAS-PR, ASAS40, BASDAI) in etanercept-</p><p> treated patients over 6 years Poddubnyy OBS 158 145  Proportion of patients not treated with </p><p>(58) TNFα inhibitors who achieved a low disease</p><p> activity state at year 2 was greater among </p><p> those with nr-axSpA</p><p> Nearly equal BASDAI scores over time</p><p> ASDAS significantly lower in nr-axSpA </p><p> patients at 2 time points Robinson (70) CP NA NA  Little variation between treatments of nr-</p><p> axSpA and AS, mostly because of the lack </p><p> of evidence on the specific nr-axSpA </p><p> treatment Sari (71) OBS 149 34  No differences in treatment efficacy Sieper (41) RCT 178 147  Similar improvements in PROs (incl. total </p><p> back pain, fatigue, and ASQoL) following </p><p> treatment with certolizumab pegol</p><p> Greater improvements in MOS-SPI in nr-</p><p> axSpA patients Sieper (72) RCT 178 147  Similar efficacy of certolizumab pegol</p><p> Rapid improvement maintained through </p><p> extension trial in both groups Song (64) RCT 20 20  Similar response rate and change in clinical </p><p> outcomes with etanercept van der RCT 121 97  Greater improvements in productivity in </p><p>Heijde (46) responders vs non-responders in AS and nr- axSpA patients treated with certolizumab </p><p> pegol</p><p> Clinical responses and clinically meaningful </p><p> improvements in PROs associated with </p><p> improved workplace and household </p><p> productivity in AS and nr-axSpA patients Use of TNFα inhibitors, n = 9 Canouï- OBS 56 26  Proportion of patients given TNFα </p><p>Poitrine (49) inhibitors was relatively low at 23% </p><p> TNFα blockers initiation was significantly </p><p> more common in AS patients Ciurea (17) OBS 838 232  Higher percentage of AS patients received </p><p>TNFα inhibitors at inclusion Kenar (54) OBS 279 100  Use of biologics in nr-axSpA patients less </p><p> common Kilic (30) OBS 155 132  Lower proportion on TNFα blockers </p><p> treatments among nr-axSpA patients Malaviya (28) OBS 193 107  Biologicals offered significantly more often </p><p> to AS patients Malaviya (36) OBS 187 101  TNFα inhibitors offered significantly more </p><p> often in the AS group at first presentation </p><p> to the clinic van der GL NA NA  ASAS 2010 guidelines </p><p>Heijde (44)  Patients with changes in SIJs on MRI but </p><p> not fulfilling the grading of SIJs on </p><p> radiographs satisfy the criteria for the start </p><p> of a TNFα inhibitor, allowing anti-TNF </p><p> treatment to start earlier in the disease course </p><p> This is a logical step, because the burden of</p><p> the disease is similar and the efficacy of </p><p>TNFα inhibitors is at least similar Wallis (40) OBS 639 73  Similar proportion of patients taking </p><p> biologic therapy Ward (43) GL NA NA  ACR guidelines 2015 update </p><p> In patients with active nr-axSpA despite </p><p> treatment with NSAIDs, TNFα inhibitors are</p><p> conditionally recommended</p><p> Other recommendations for nr-axSpA were</p><p> the same as for AS (based on indirect </p><p> evidence) Use of other treatments, n = 8 Kilic (30) OBS 155 132  Patients with nr-axSpA used NSAIDs (80%), </p><p> sulfasalazine (19%), and MTX (3%); in AS </p><p> patients these ratios were 74%, 26%, and </p><p>1%, respectively Malaviya (28) OBS 193 107  Low-dose MTX, as monotherapy or in </p><p> combination with other DMARDs, was </p><p> prescribed more often in nr-axSpA </p><p> patients, possibly due to initial </p><p> misdiagnosis of nr-axSpA as rheumatoid </p><p> arthritis Malaviya (36) OBS 187 101  MTX was offered more often to nr-axSpA </p><p> patients Poddubnyy OBS 214 214  DMARD and NSAID intake similar (58)  Small proportions of patients in both </p><p> groups achieved low disease activity </p><p> without TNFα inhibitor therapy; proportion</p><p> was greater among nr-axSpA patients when</p><p> outcome measures that included the CRP </p><p> were used Robinson (70) CP NA NA  Little variation between treatments of nr-</p><p> axSpA and AS, mostly because of the lack </p><p> of evidence on the specific nr-axSpA </p><p> treatment van der GL NA NA  ASAS 2010 guidelines </p><p>Heijde (44)  Mandatory pretreatment with ≥2 NSAIDs </p><p> for ≥4 weeks before TNFα inhibitors can be </p><p> started</p><p> Patients with axial symptoms require no </p><p> further pretreatment; patients with </p><p> symptomatic peripheral symptoms should </p><p> have an adequate trial treatment with a </p><p>DMARD, preferably sulfasalazine Wallis (40) OBS 639 73  Similar proportions of patients treated with</p><p>NSAIDS, DMARDS, and glucocorticoids Ward (43) GL NA NA  ACR guidelines 2015 update </p><p> Recommendations for nr-axSpA were the </p><p> same as for AS (based on indirect evidence) Adherence, n = 3 Corli (53) OBS 263 98  No significant difference in drug survival of </p><p>TNFα inhibitors Lubrano (57) OBS 259 62  Overall rate of discontinuation after the </p><p> first TNFα inhibitor was 11.2% (n = 7) in nr-</p><p> axSpA and 18.5% (n = 48) in AS patients Sari (71) OBS 149 34  BASMI associated with lower response to </p><p>TNFα inhibitors *ACR = American College of Rheumatology; AS = ankylosing spondylitis; ASAS = Assessment of SpondyloArthritis international Society; ASAS-PR = Assessment of SpondyloArthritis international Society Partial Remission; ASDAS = </p><p>Ankylosing Spondylitis Disease Activity Score; ASDAS CII = Ankylosing Spondylitis Disease Activity Score Clinically </p><p>Important Improvement; ASDAS ID = Ankylosing Spondylitis Disease Activity Score Inactive Disease; ASDAS MI = </p><p>Ankylosing Spondylitis Disease Activity Score Major Improvement; ASQoL = Ankylosing Spondylitis Quality of Life; </p><p>BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BASFI = Bath Ankylosing Spondylitis Functional Index; </p><p>CP = consensus paper; CRP = C-reactive protein; DMARD = disease-modifying antirheumatic drug; GL = guideline; </p><p>MOS-SPI = Medical Outcomes Study Sleep Problems Index; MRI = magnetic resonance imaging; MTX = methotrexate; NA = not applicable; NR = not reported; nr-axSpA = non-radiographic axial spondyloarthritis; NSAID </p><p>= non-steroidal anti-inflammatory drug; OBS = observational study; PRO = patient-reported outcome; SIJ = sacroiliac joint; TNF = tumor necrosis factor.</p>