Supplemental Table 4 . Literature Identified on Treatment Efficacy in Nr-Axspa Versus AS

Supplemental Table 4. Literature identified on treatment efficacy in nr-axSpA versus AS

Primary Study AS nr-axSpA Relevant findings author design patients patients

(reference) (n) (n) Treatment efficacy, n = 14 Callhoff (42) Meta- NR NR  Lower effect sizes of TNFα blockers on

analysis BASDAI and BASFI in nr-axSpA patients Ciurea (17) OBS 565 161  Response rate (BASDAI50, ASDAS CII,

ASDAS MI, ASDAS ID, ASAS-PR) to TNFα

inhibitors not significantly higher in AS

patients

 ASAS40 significantly higher in AS patients Corli (53) OBS 263 98  Treatment response, drug survival, and

patient outcomes after initiation of first-

line TNFα inhibitor similar

 BASDAI20 and BASDAI50 of TNFα inhibitors

at 12 months not significantly different Landewé (31) RCT 178 147  ASAS20, ASAS40, and ASDAS after

treatment with certolizumab pegol similar Lubrano (57) OBS 259 62  Probability of obtaining partial remission

during treatment with TNFα inhibitors not

significantly different

 Partial remission significantly associated

with the absence of peripheral arthritis,

enthesitis, and psoriasis at baseline in

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

(69) (ASAS-PR, ASAS40, BASDAI) in etanercept-

treated patients over 6 years Poddubnyy OBS 158 145  Proportion of patients not treated with

(58) TNFα inhibitors who achieved a low disease

activity state at year 2 was greater among

those with nr-axSpA

 Nearly equal BASDAI scores over time

 ASDAS significantly lower in nr-axSpA

patients at 2 time points Robinson (70) CP NA NA  Little variation between treatments of nr-

axSpA and AS, mostly because of the lack

of evidence on the specific nr-axSpA

treatment Sari (71) OBS 149 34  No differences in treatment efficacy Sieper (41) RCT 178 147  Similar improvements in PROs (incl. total

back pain, fatigue, and ASQoL) following

treatment with certolizumab pegol

 Greater improvements in MOS-SPI in nr-

axSpA patients Sieper (72) RCT 178 147  Similar efficacy of certolizumab pegol

 Rapid improvement maintained through

extension trial in both groups Song (64) RCT 20 20  Similar response rate and change in clinical

outcomes with etanercept van der RCT 121 97  Greater improvements in productivity in

Heijde (46) responders vs non-responders in AS and nr- axSpA patients treated with certolizumab

 Clinical responses and clinically meaningful

improvements in PROs associated with

improved workplace and household

productivity in AS and nr-axSpA patients Use of TNFα inhibitors, n = 9 Canouï- OBS 56 26  Proportion of patients given TNFα

Poitrine (49) inhibitors was relatively low at 23%

 TNFα blockers initiation was significantly

more common in AS patients Ciurea (17) OBS 838 232  Higher percentage of AS patients received

TNFα inhibitors at inclusion Kenar (54) OBS 279 100  Use of biologics in nr-axSpA patients less

common Kilic (30) OBS 155 132  Lower proportion on TNFα blockers

treatments among nr-axSpA patients Malaviya (28) OBS 193 107  Biologicals offered significantly more often

to AS patients Malaviya (36) OBS 187 101  TNFα inhibitors offered significantly more

often in the AS group at first presentation

to the clinic van der GL NA NA  ASAS 2010 guidelines

Heijde (44)  Patients with changes in SIJs on MRI but

not fulfilling the grading of SIJs on

radiographs satisfy the criteria for the start

of a TNFα inhibitor, allowing anti-TNF

treatment to start earlier in the disease course

 This is a logical step, because the burden of

the disease is similar and the efficacy of

TNFα inhibitors is at least similar Wallis (40) OBS 639 73  Similar proportion of patients taking

biologic therapy Ward (43) GL NA NA  ACR guidelines 2015 update

 In patients with active nr-axSpA despite

treatment with NSAIDs, TNFα inhibitors are

conditionally recommended

 Other recommendations for nr-axSpA were

the same as for AS (based on indirect

evidence) Use of other treatments, n = 8 Kilic (30) OBS 155 132  Patients with nr-axSpA used NSAIDs (80%),

sulfasalazine (19%), and MTX (3%); in AS

patients these ratios were 74%, 26%, and

1%, respectively Malaviya (28) OBS 193 107  Low-dose MTX, as monotherapy or in

combination with other DMARDs, was

prescribed more often in nr-axSpA

patients, possibly due to initial

misdiagnosis of nr-axSpA as rheumatoid

arthritis Malaviya (36) OBS 187 101  MTX was offered more often to nr-axSpA

patients Poddubnyy OBS 214 214  DMARD and NSAID intake similar (58)  Small proportions of patients in both

groups achieved low disease activity

without TNFα inhibitor therapy; proportion

was greater among nr-axSpA patients when

outcome measures that included the CRP

were used Robinson (70) CP NA NA  Little variation between treatments of nr-

axSpA and AS, mostly because of the lack

of evidence on the specific nr-axSpA

treatment van der GL NA NA  ASAS 2010 guidelines

Heijde (44)  Mandatory pretreatment with ≥2 NSAIDs

for ≥4 weeks before TNFα inhibitors can be

started

 Patients with axial symptoms require no

further pretreatment; patients with

symptomatic peripheral symptoms should

have an adequate trial treatment with a

DMARD, preferably sulfasalazine Wallis (40) OBS 639 73  Similar proportions of patients treated with

NSAIDS, DMARDS, and glucocorticoids Ward (43) GL NA NA  ACR guidelines 2015 update

 Recommendations for nr-axSpA were the

same as for AS (based on indirect evidence) Adherence, n = 3 Corli (53) OBS 263 98  No significant difference in drug survival of

TNFα inhibitors Lubrano (57) OBS 259 62  Overall rate of discontinuation after the

first TNFα inhibitor was 11.2% (n = 7) in nr-

axSpA and 18.5% (n = 48) in AS patients Sari (71) OBS 149 34  BASMI associated with lower response to

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 =

Ankylosing Spondylitis Disease Activity Score; ASDAS CII = Ankylosing Spondylitis Disease Activity Score Clinically

Important Improvement; ASDAS ID = Ankylosing Spondylitis Disease Activity Score Inactive Disease; ASDAS MI =

Ankylosing Spondylitis Disease Activity Score Major Improvement; ASQoL = Ankylosing Spondylitis Quality of Life;

BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BASFI = Bath Ankylosing Spondylitis Functional Index;

CP = consensus paper; CRP = C-reactive protein; DMARD = disease-modifying antirheumatic drug; GL = guideline;

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

= non-steroidal anti-inflammatory drug; OBS = observational study; PRO = patient-reported outcome; SIJ = sacroiliac joint; TNF = tumor necrosis factor.