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1 RHEUMATOLOGY Rheumatology 2017;56: doi: /rheumatology/kew473 Advance Access publication 7 January 2017 CLINICAL SCIENCE Original article Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-tnf therapy: a population-based regional cohort study from southern Sweden Johan K. Wallman 1,2, *, Anna Jöud 3, *, Tor Olofsson 1,2, Lennart T. H. Jacobsson 4, Henning Bliddal 5 and Lars E. Kristensen 1,5 Abstract Objective. The aim was to assess work-loss days before and after commencement of anti-tnf treatment in patients with non-radiographic axial spondylarthritis (nr-axspa). Methods. Bionaïve nr-axspa patients (n = 75), aged years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-tnf treatment during , were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-tnf initiation. Matched population references were included for comparison and to adjust for secular trends. Results. The nr-axspa patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-tnf initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axspa group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Conclusion. Anti-TNF therapy in nr-axspa was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up. Key words: anti-tnf treatment, biologic treatment, spondyloarthritis, non-radiographic axial spondyloarthritis, work disability, sick leave, disability pension Rheumatology key messages. Following anti-tnf start in non-radiographic axial SpA, a significant and sustained decrease in sick leave was observed.. Disability pension level among non-radiographic axial SpA patients was similar to the general population throughout.. Despite the improvement, the non-radiographic axial SpA patients work-loss day level remained twice that of the general population. 1 Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden, 2 Department of Rheumatology, Skåne University Hospital, Lund, Sweden, 3 Division of Occupational and Environmental Medicine, Department of Laboratory Medicine Lund, Lund University, Lund, Sweden, 4 Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden and 5 The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Frederiksberg and Bispebjerg, Denmark Submitted 16 June 2016; revised version accepted 28 November 2016 *Johan K. Wallman and Anna Jöud contributed equally to this study Correspondence to: Johan K. Wallman, Reumatologiska kliniken, Kioskgatan 3, Lund, Sweden. johan.81.karlsson@gmail.com! The Author Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please journals.permissions@oup.com

2 Anti-TNF effect on work-loss days in nr-axspa Introduction Spondyloarthritis encapsulates a group of conditions with similar axial (sacroiliitis/spondylitis) and/or peripheral (arthritis/enthesitis/dactylitis) muskuloskeletal symptoms and an association with HLA-B27. While AS, the archetypal form of axial spondyloarthritis, is defined by radiographic sacroiliitis [1], many patients display similar symptoms and sacroiliacal joint inflammation on MRI without such X-ray changes [2]. Therefore, in 2009, the Assessment of SpondyloArthritis international Society (ASAS) validated novel classification criteria for axial spondyloarthritis [3], encompassing patients both with (AS) and without radiographic sacroiliitis; the latter group henceforth known as non-radiographic axial spondyloarthritis (nr-axspa). Studies comparing nr-axspa and AS have found a similar burden of disease, and treatment recommendations are also alike [2, 4 10]. In AS, where proportions of work-disabled subjects range from 5 to 35% [11], anti- TNF therapy has been repeatedly shown to improve work disability [12 15], whereas this has hitherto been very sparsely studied in nr-axspa. In short-term randomized controlled trials, clinical response to either anti- TNF or placebo in nr-axspa has been associated with favourable work-related outcomes [16, 17]. Significant anti-tnf effects on self-reported at-work productivity (presenteeism) have also been demonstrated, whereas results are less consistent regarding work-loss days (absenteeism) [18]. Results based on prospectively recorded register data are, however, lacking. In the present study, we thus aimed to describe the development of work-loss days, attributable to sick leave and/or disability pension, in nr-axspa from 1 year before to 2 years after anti-tnf initiation, and to compare this with matched population references. Predictors of work-loss days after anti-tnf start were also assessed. Methods Settings and data sources Linkage of data from the following sources was accomplished using the personal identification number, unique to every Swedish citizen. South Swedish Arthritis Treatment Group register The South Swedish Arthritis Treatment Group (SSATG) register is an observational register study involving 12 rheumatology units, in which chronic arthritis patients commencing treatment with biologic DMARDs in southern Sweden were prospectively monitored according to a structured protocol starting in 1999 [19]. Swedish Social Insurance Agency register and work disability compensation system The Swedish Social Insurance Agency (SSIA) provides financial protection for individuals of working age (16 64 years) in connection with sickness, disability or injury and covers everyone who legally lives or works in Sweden. Compensations are granted in the form of sick leave or, in the event of longstanding inability to work, disability pension, both of which may be granted for 25, 50, 75 or 100% of full working time, and the two compensation types may be combined in the same day (although never exceeding 100%; e.g. 25% disability pension and 75% sick leave). For sick leave, the first day of absence (the qualifying day) is not compensated and days 2 14 are reimbursed by the employer. Short-term sick leave periods 4 14 days are thus not administered by the SSIA, whereas all workloss periods (sick leave and/or disability pension) exceeding 2 weeks are continuously and prospectively recorded in the SSIA register, from which day-level data on these compensations may be retrieved. Moreover, if a new sick leave period starts within 5 days of another, they are counted together, and once exceeding 14 days the first 2 weeks are also recorded in the SSIA register. In Sweden, it is also possible to be on sick leave as unemployed if you are considered unable to perform any kind of work on the labour market. Swedish Population Register The population register is a national register containing individual statistics of vital events such as births, deaths, marriages, divorces, migrations and residential addresses. The register is administrated by the Swedish Tax Agency. Study population Bionaïve nr-axspa patients aged years, monitored at the Department of Rheumatology, Skåne University Hospital and commencing anti-tnf treatment during , were retrieved from the observational SSATG study (n = 75; patient inclusion flow chart provided in Fig. 1). All patients had a clinical diagnosis of undifferentiated axial spondyloarthritis and, based on retrospective analysis of data collected at anti-tnf initiation, fulfilled the ASAS criteria for axial spondyloarthritis, without skin psoriasis or radiographic sacroiliitis (n[asas criteria imaging/ clinical arms] = 43/32; modified New York criteria negative X-rays available for all; inflammatory sacroiliitis on MRI defined according to clinical practice) [1, 3]. In Sweden, anti-tnf agents were often used to treat patients with the nr-axspa phenotype, even before this diagnosis was formally characterized in 2009, explaining the early treatment start dates in our cohort. For each patient, four population references matched for age, sex and municipality were randomly selected from the Swedish Population Register, in order to relate work-loss days in the nraxspa group to the background population level and to control for secular trends. Outcome variables Day-level data on work-loss days attributable to sick leave and/or disability pension (excluding periods 4 14 days) for patients and population references were retrieved from the SSIA, covering 360 days before to 720 days after anti-tnf initiation (or for the references, the anti- TNF start date of their index patients) or until the individual 717

3 Johan K. Wallman et al. FIG. 1Flow chart describing the patient inclusion a Patients in the SSATG register with a clinical diagnosis of PsA were not screened for inclusion in the present study. In conformity with this, we also decided to exclude two patients with axial PsA. b In comparison with the study population (n = 75), the 44 subjects with insufficient data for classification were significantly older [median (interquartile range; range) age: 47 (18; 20 67) years] and had longer disease duration [11 (14; 1 42) years], whereas no difference was observed regarding sex, prior presence of peripheral arthritis, patient s VAS global/pain, BASDAI, BASFI, Evaluator s global, ESR or CRP scores at anti-tnf initiation (comparisons by 2 test for categorical and Mann Whitney U-test for continuous variables). ASAS: Assessment of SpondyloArthritis international Society; nr-axspa: non-radiographic axial spondyloarthritis; SSATG: South Swedish Arthritis Treatment Group; VAS: visual analog scale. died. All work-loss days were included, irrespective of the cause; that is, for the patients, the recorded work disability could be related (directly or indirectly) or unrelated to nr-axspa. The outcome variables studied were net days during each quarter of a year (90 days) of sick leave, disability pension and the combination of both (referred to as work-loss days). One net day corresponds to a full day of work-loss; for example, 4 days with 25% sick leave or 1 day with 75% disability pension and 25% sick leave. Predictors of work-loss days from 6 months to 2 years after anti-tnf initiation in the nr-axspa group were also studied, as described in the statistics subsection below. Informed consent was given by all patients before entry in the SSATG register study. Cross-linking of SSIA and health-care data was approved by the ethical committee in Lund (no. 514/2007). Exposures Anti-TNF therapy was started because of high disease activity and inadequate response or intolerance to one or more NSAIDs. Treatment decisions were taken by the responsible rheumatologists, and no formal disease activity level was required for anti-tnf initiation, although the 718

4 Anti-TNF effect on work-loss days in nr-axspa indication was supported by guidelines when they began to emerge [9]. Apart from infliximab, which was started at 3 mg/kg, with possible dose increments to a maximum of 500 mg every 4 8 weeks, anti-tnf dosages were in general as recommended by the manufacturers. Patients could receive NSAIDs, low-dose oral glucocorticoids, intra-articular glucocorticoids and conventional DMARDs both prior to and during the study period according to clinical practice; the latter mainly applied for peripheral arthritis. Statistics Work-loss days Owing to skewed distributions, the sick leave, disability pension and work-loss day levels between different follow-up periods within the nr-axspa group were compared by the Wilcoxon matched-pair signed-rank test. Mean (95% CI) differences in the same outcomes between the nr-axspa patients and population references were estimated by analysis of variance, accounting for the matched design and applying non-parametric bootstrapping to calculate CIs. Predictor analyses Predictors of cumulative net work-loss days (sick leave plus disability pension) from 6 months to 2 years after anti-tnf initiation (days ) in the nr-axspa group were assessed by multivariate regression, using nonparametric bootstrapping to estimate CIs. Logistic regression with any work-loss days (n [yes/no] = 27/48) during the same period as outcome was also performed. The first 6 months following anti-tnf initiation was omitted from the outcome period, because we aimed to study predictors of future work-loss days rather than baseline associations (thus allowing 6 months for potential anti-tnf effects to stabilize). The following potential predictors at anti-tnf initiation were identified based on subject matter knowledge: sex, age, disease duration, prior presence of peripheral arthritis (yes/no), inflammatory sacroiliitis on MRI (yes/no, defined according to clinical practice), CRP elevation (>3 mg/l; yes/no), anti-tnf start year ( ), net work-loss days during the final quarter before anti-tnf start (0 90 days) and scores of patient s visual analog scales for global health and pain (VAS global; VAS pain), evaluator s global assessment on a five-grade Likert scale (Evaluator s global), BASDAI and BASFI. Beyond these baseline variables, anti-tnf adherence 4 6 months (i.e. ceasing treatment prior to the outcome period) was also assessed. Owing to the limited number of patients (n = 75), only the seven of these potential predictors with the highest Spearman correlation to the continuous outcome (i.e. cumulative net work-loss days) were included in the final models (applying the same variables in both the linear and logistic regressions). In the event of multicollinearity (Spearman s r or 0.4 or less), the variable with the least correlation to the outcome was, however, omitted. Apart from this strategy, based on subject matter TABLE 1 Patient characteristics at anti-tnf initiation knowledge, we also decided to retain disease duration and CRP elevation in the analyses. When entering disease duration, age was omitted owing to multicollinearity, and with respect to the number of patients per covariate, the MRI variable (with the lowest correlation to the outcome of those originally included) was instead omitted when entering CRP elevation. All analyses were performed using International Business Machines Corporation s (IBM) Statistical Package for the Social Sciences (SPSS) version 20 or StataCorp s Stata version Results Characteristics n = 75 Male sex, n (%) 47 (63) Age, years Median (IQR) 35 (28 44) Range Disease duration, years Median (IQR) 6 (2 11) Range Peripheral arthritis, n (%) 31 (41) Inflammatory sacroiliitis 43 (65) on MRI, n (%) VAS global, mm 59 (19) VAS pain, mm 60 (22) BASDAI 5.3 (1.7) BASFI 4.1 (2.3) Evaluator s global, (0.6) ESR, mm/h 22 (20) CRP, mg/l 10 (13) Elevated CRP, n (%) 41 (58) Concomitant DMARD, n (%) 21 (28) Previous DMARDs, n Median (IQR) 0 (0 1) Range 0 3 Initial anti-tnf therapy, n (%) Infliximab 16 (21) Etanercept 31 (41) Adalimumab 18 (24) Golimumab 7 (9) Certolizumab pegol 3 (4) Full-time disability pension at 2 (3) anti-tnf start, n (%) Values are given as the mean (S.D.) unless otherwise stated. Missing data, n (%): disease duration 1 (1), MRI 9 (12), VAS global/pain 7 (9), BASDAI 30 (40), BASFI 29 (39), Evaluator s global 2 (3), ESR 3 (4), CRP 4 (5), and concomitant DMARD 1 (1). BASDAI and BASFI measurements were not mandatory within the SSATG during the study period, explaining the relatively high numbers of missing data for these parameters. IQR: interquartile range; SSATG: South Swedish Arthritis Treatment Group study; VAS: visual analog scale. Patient characteristics and anti-tnf adherence Patient characteristics at anti-tnf initiation are presented in Table 1. No patient died during the follow-up period

5 Johan K. Wallman et al. FIG. 2Developments of sick leave, disability pension and work-loss days Developments of mean (95% CI) days per quarter of a year (90 days) of sick leave (A), disability pension (B) and work-loss days (C) in the nr-axspa group and population references from 1 year before to 2 years after anti-tnf initiation. The table below the graphs shows the mean (95% CI) difference in the respective outcomes between the nr-axspa patients and references at key time points. *P < 0.05 and **P < 0.01 for change within the nr-axspa group. Data for all 75 nr-axspa patients were available for every quarter. One reference person died and did not contribute data for quarters 6 8. NraxSpA, non-radiographic axial spondyloarthritis; NS, non-significant. Allowing anti-tnf switches with 43 months from ceasing one agent to starting another, 72% of patients remained on anti-tnf therapy throughout the 2-year follow-up (60% on their initial treatment and 12% having switched once). By the same definition, the mean (S.D.) anti-tnf adherence time was 20 (7) months. Work-loss days In the year before anti-tnf initiation, the mean quarterly days of sick leave among the nr-axspa patients increased significantly, peaking at 18.2 days more than among the population references in the quarter immediately after the start of treatment. Following anti-tnf initiation, the mean number of quarterly sick leave days then steadily (and significantly) declined during the 2-year follow-up, although remaining statistically higher than among the references throughout (Fig. 2A). Meanwhile, the disability pension level among the nr-axspa patients did not differ from that of the population references at any time point (Fig. 2B). Added together, during the 2 years from anti-tnf initiation, the mean quarterly number of work-loss days decreased significantly from a peak at 16.5 days to 6.8 days more than in the population references (Figs 2C and 3). As expected, the absence of any work-loss days from 6 months to 2 years after anti-tnf start was associated with consistently better point estimate means for clinical parameters during follow-up, as compared with patients with 51 work-loss day during the same period (Table 2). Predictors of work-loss days after anti-tnf initiation Higher work-loss day levels immediately before anti-tnf initiation and chronologically earlier anti-tnf start years significantly predicted more work-loss days during the outcome period (Table 3). In the logistic analysis, female sex, longer disease duration and, again, higher levels of baseline work-loss were associated with the occurance of any work-loss days during follow-up (Table 3). Discussion Main findings This population-based cohort study provides evidence of a significant and sustained decrease in sick leave among nr-axspa patients after anti-tnf treatment initiation. Despite the improvement, however, the mean number of sick leave days still remained significantly higher than among the population references at the end of followup. In contrast, similar levels of disability pension were observed among the nr-axspa patients and references throughout. Overall, during 2 years from anti-tnf initiation, the mean quarterly work-loss days in the nraxspa group decreased from 3.4 to 1.9 times more than in the general population. Previous research Work-loss days In a 6-month randomized controlled trial, etanercept treatment failed to show any impact on self-reported work-loss 720

6 Anti-TNF effect on work-loss days in nr-axspa TABLE 2 Clinical parameters in relationship to any work-loss day status Anti-TNF start 6 months 24 months Characteristics No work-loss days Work-loss days 51 No work-loss days Work-loss days 51 No work-loss days Work-loss days 51 VAS global (mm) 58 (19) 60 (19) 31 (27) 33 (26) 24 (24) a 46 (25) VAS pain (mm) 60 (23) 61 (21) 31 (28) 31 (23) 23 (25) a 46 (27) BASDAI 5.1 (1.6) 5.6 (1.9) 3.1 (2.9) 4.5 (2.7) 1.9 (1.9) 4.0 (3.2) BASFI 4.1 (2.1) 4.1 (2.5) 2.4 (2.8) 3.5 (2.4) 1.2 (1.5) 3.5 (3.0) Evaluator s global (0 4) 1.8 (0.6) 1.7 (0.6) 0.6 (0.8) 0.8 (0.6) 0.6 (0.7) 0.9 (0.5) ESR (mm/h) 21 (22) 23 (15) 6.2 (3.9) a 12.2 (8.0) 8.9 (9.6) 9.8 (6.3) CRP (mg/l) 10 (14) 8.3 (11.3) 2.3 (3.3) 4.4 (6.7) 2.2 (3.1) 2.7 (3.1) Values are given as the mean (S.D.). Clinical parameters are shown in relationship to any work-loss day status from 6 months to 2 years after anti-tnf initiation in patients with non-radiographic axial spondylarthritis. No work-loss days, n = 48; work-loss days 51, n = 27. a P < 0.05 vs the work-loss days 51 group by Mann Whitney U-test. Missing data n (%): VAS global/pain 7 (9) at anti-tnf start, 33 (44) at 6 months and 36 (48) at 24 months; BASDAI 30 (40), 58 (77) and 51 (68); BASFI 29 (39), 58 (77) and 51 (68); Evaluator s global 2 (3), 33 (44) and 36 (48); ESR 3 (4), 36 (48) and 42 (56); and CRP 4 (5), 34 (45) and 39 (52). VAS: visual analog scale. TABLE 3 Predictors of cumulative work-loss days and any work-loss days Characteristics days, whereas presenteeism improved significantly more than with placebo [18]. In other short-term trials, both these outcomes have, however, been shown to improve more among clinical responders (vs non-responders) to either anti-tnf therapy or placebo, although less consistently so regarding work-loss days [16, 17]. Apart from this, data regarding work disability in nr-axspa remain sparse [7]. In AS, in contrast, work-loss day levels are well known to exceed those of the general population [11, 20], and several studies have demonstrated beneficial effects thereon of anti-tnf therapy [12 15]. Comparing the present results with a previous AS study from the same region [14], similar baseline levels and 1-year improvements of sick leave were observed, whereas disability pension was around four times more common among the AS patients, potentially reflecting the older age and more Cumulative work-loss days Multivariate linear regression Any work-loss days Multivariate logistic regression B (95% CI) P-value OR (95% CI) P-value Male (vs female) 32 ( 108, 44) (0.03, 0.99) Age, per year 1 ( 1, 4) (0.99, 1.16) Disease duration, per year a 3( 1, 6) (1.01, 1.26) Peripheral arthritis, yes/no 43 ( 18, 104) (0.67, 24.21) Inflammatory sacroiliitis on MRI, yes/no 0 ( 57, 58) (0.05, 2.81) Elevated baseline CRP, yes/no b, c 46 ( 100, 8) (0.08, 2.77) Anti-TNF start year, per year ( 42, 7) (0.58, 1.52) Anti-TNF adherence 46 months, yes/no 61 ( 39, 160) (0.07, 22.64) Baseline work-loss, per day 0 90 d 3 (2, 4) < (1.03, 1.10) Predictors of cumulative work-loss days and any work-loss days from 6 months to 2 years after anti-tnf initiation in patients with nr-axspa. a Analysed in separate models from age owing to multicollinearity. b CRP at anti-tnf initiation >3 mg/l. c Analysed in separate models from the MRI variable with respect to the number of patients per covariate. d Number of work-loss days during the quarter of a year immediately before anti-tnf initiation. Missing data, n (%): disease duration 1 (1), MRI 9 (12) and CRP 4 (5). B: b estimate; OR: odds ratio. longstanding disease in this group [mean (S.D.) age, AS/ nr-axspa: 41 (10)/37 (11) years; disease duration, AS/nraxSpA: 14 (11)/8 (8) years]. Predictor analyses Although previous data remain scant for nr-axspa, a large number of factors have been associated with future work disability in patients with AS, with manual labour professions and worse scores for pain and physical disability (including BASFI) being among the most consistently reported [11]. In a recently published cohort study following AS patients for 12 years, adverse work outcomes were again predicted by higher BASFI scores at baseline, but also by worsening disease activity (BASDAI) and function (BASFI) over time, as well as by new occurrence of uveitis or IBD during follow-up [21]. Work disability in AS also 721

7 Johan K. Wallman et al. FIG. 3Distributions of work-loss days in the nr-axspa group Distributions of work-loss days (as a percentage) per quarter of a year (90 days) in the nr-axspa group from 1 year before to 2 years after anti-tnf initiation. Data for all 75 nr-axspa patients were available for every quarter. Nr-axSpA, nonradiographic axial spondyloarthritis. appears to increase with longer disease duration, although in relationship to age-matched population references the differences are most pronounced for younger patients [11]. With regard to sex, the available AS data are less consistent [11]. The finding that a higher level of baseline work-loss was associated with more (as well as any) work-loss days during follow-up was not unexpected and is supported by similar data from early RA, where this was identified as the strongest risk factor for more work-loss days during 3 years from diagnosis [22]. In analogy with this, worse levels of presenteeism have also been shown to predict future sick leave in patients with AS [23]. Whether an earlier anti-tnf intervention during the disease course of nr-axspa would reduce future work-loss days cannot be concluded from the present data. The binary association observed with disease duration (although not controlled for age), as well as the better outcome seen in patients who have not already progressed to stages with more work-loss days before the start of treatment, may, however, both be interpreted to point in this direction. Finally, the observed association between anti-tnf start year and cumulative work-loss days is likely to reflect the stricter regulation of Swedish work disability compensations during later years, as well as a secular trend towards the use of anti-tnf therapy in less severely ill patients. Strengths and limitations The objective assessment of work-loss days by an external source, rather than self-reported questionnaires, is a major strength of the present study, which is, to our knowledge, also the first to demonstrate a significant and sustained impact of anti-tnf therapy on work-loss days in nr-axspa. Limitations encompass a lack of presenteeism data and the exclusion of sick leave periods 4 14 days, which are not recorded by the SSIA. The retrospective classification of patients according to the ASAS criteria for axial spondyloarthritis may have limited study inclusion, because all relevant data could not be retrieved for all the screened subjects (Fig. 1). Furthermore, the open, observational setting naturally has limitations in its internal validity, such as possible bias regarding patients selected for treatment, assignment of treatment and collection of clinical data. The study outcomes were, however, collected from an independent and blinded source (the SSIA) for both patients and population references, and are of high quality because they are linked to the payment system. Regarding the predictor analyses, the relatively low power (n = 75) may have limited our ability to demonstrate significant associations with some of the studied variables, whereas a lack of data prevented us from including other potential predictors, such as profession, co-morbidity status, presenteeism and coping strategies. Conclusions In patients with nr-axspa, anti-tnf therapy was associated with a significant and sustained decrease in work-loss days during 2 years from treatment initiation. The decline was seen for sick leave, whereas disability pension rates remained similar to those of the general population throughout. Despite the decrease, the proportion of work-loss days was still twice as high as in the general population at the end of follow-up. Acknowledgements We are indebted to all patients, colleagues and staff involved in the SSATG register study. Dr Kristensen and 722

8 Anti-TNF effect on work-loss days in nr-axspa Dr Bliddal have received research support from the Oak Foundation. The sponsors had no role in study design, data collection, data analysis, data interpretation or writing of the report. Contributors: L.E.K. (guarantor), J.K.W. and A.J. participated in study design, acquisition of data, draft and revision of the manuscript, analysis and interpretation of data. T.O., L.T.H.J. and H.B. participated in study design, interpretation of data and revision of the manuscript. All authors read and approved the final manuscript. All authors ensured that data have been handled with accuracy and integrity to the extent possible. Funding: This work was supported by Region Skåne, Lund University Hospital, the Swedish Research Council, the Faculty of Medicine at Lund University, the Österlund Foundation, the Kock Foundation, the Swedish Rheumatism Association and King Gustav V 80-year fund. Disclosure statement: J.K.W. reported participating in advisory boards for Novartis and Celgene and has received consultancy fees from Union Chimique Belge (UCB) (all unrelated to the current work). L.E.K., L.T.H.J. and H.B. have received fees for speaking and consultancy from Pfizer, Novartis, Union Chimique Belge, Abbvie, Celgene, Bristol-Myers Squibb and Merck Sharpe Dome (MSD). A.J. has received fees for speaking from Pfizer. T.O. has nothing to declare. No authors have any nonfinancial disclosures. References 1 van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27: Rudwaleit M, Haibel H, Baraliakos X et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 2009;60: Rudwaleit M, van der Heijde D, Landewe R et al. 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9 Johan K. Wallman et al. 21 Castillo-Ortiz JD, Ramiro S, Landewé R et al. Work outcome in patients with ankylosing spondylitis: results from a 12-year followup of an international study. Arthritis Care Res 2016;68: Olofsson T, Petersson IF, Eriksson JK et al. Predictors of work disability during the first 3 years after diagnosis in a national rheumatoid arthritis inception cohort. Ann Rheum Dis 2014;73: Tran-Duy A, Nguyen TT, Thijs H et al. Longitudinal analyses of presenteeism and its role as a predictor of sick leave in patients with ankylosing spondylitis. Arthritis Care Res 2015;67: Clinical vignette Regression of microangiopathy in antisynthetase syndrome FIG. 1(A) Capillaroscopy at baseline: giant ramified capillaries, derangement of the vascular array and loss of capillary density. (B) The same areas after treatment: hairpin-shaped or slightly abnormal capillaries and normal capillary density. Rheumatology 2017;56:724 doi: /rheumatology/kew425 Advance Access publication 9 December 2016 A 69-year-old woman with progressive proximal muscle weakness, shortness of breath, RP and digital ulcerations was admitted to our department in February CRP and creatine kinase were elevated and anti-pl12 antibodies were present. EMG showed signs of myopathy and chest high-resolution CT revealed interstitial lung disease. In nailfold videocapillaroscopy (NVC), giant ramified capillaries and loss of capillary density were observed (Fig. 1A). Based on clinical and laboratory findings, a diagnosis of antisynthetase syndrome was made. The patient was started on methylprednisolone, AZA and i.v. prostanoids with good clinical response. Followup in July 2016 found no muscle weakness, digital ulcerations were healed and biochemical markers were within normal limits. There was also a slight improvement of in the diffusing capacity of the lungs for carbon monoxide from 36 to 43%. NVC showed remarkable regression of microvascular damage, with an increase in capillary density, restoration of hairpin-shaped capillary loops and signs of neoangiogenesis (Fig. 1B). In the presented case, the resolution of clinical symptoms and improvement in lung function were mirrored by the evolution of severe microangiopathy into an almost normal capillary image, which makes NVC a potential tool for monitoring treatment response. Moreover, our findings are consistent with a recently proposed DM pattern [1], which may further aid early diagnosis of inflammatory myopathies, such as antisynthetase syndrome. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest. Marek M. Chojnowski 1 and Jolanta Nałęcz-Janik 1 1 Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland Correspondence to: Marek M. Chojnowski, Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartanska 1, Warsaw, Poland. marekchojnowski84@gmail.com Reference 1 Manfredi A, Sebastiani M, Campomori F et al. Nailfold videocapillaroscopy alterations in dermatomyositis and systemic sclerosis: toward identification of a specific pattern. J Rheumatol 2016;43: ! The Author Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please journals.permissions@oup.com 724