The relationship of cervicothoracic mobility restrictions to fall risk and fear of falling in ankylosing spondylitis.

Objective: The objective of this study is to determine whether restricted cervical mobility in ankylosing spondylitis (AS) is associated with increased fall frequency or fear of falling. Methods: A total of 134 AS patients and 199 age- and gender-matched control subjects (CS) with soft-tissue cervicothoracic pain were prospectively evaluated for fall risk. Subjects were divided into non-fallers, single fallers, and multiple fallers. Dynamic cervical rotations and static cervicothoracic axial measurements were compared between the groups. In total, 88 AS patients were reviewed more than once; Kaplan-Meier plots were constructed for fall risk as a function of cervical rotation amplitudes. Falls Efficacy Scale-International (FES-I) questionnaire measured the fear of falling. Results: In total, 34% of AS patients and 29% of CS fell (p = 0.271) in the year prior to evaluation. In AS, static anatomical measurements were unrelated to fall occurrence. The trends of multiple AS fallers to greater flexed forward postures and reduced dynamic cervical rotations were not statistically significant. Cervicothoracic pain (p = 0.0459), BASDAI (p = 0.002), and BASFI (p = 0.003) scores were greater in multiple fallers. FES-I scores were greater in fallers (p = 0.004). Of the 88 AS patients reviewed (or seen) on more than one occasion, 46.5% fell over the 9-year observation period, including all multiple fallers and 71.4% of single fallers. Survival curves showed increased fall risk as cervical rotational amplitudes decreased. Conclusion: In AS, decreased cervical rotations increase fall risk and fear of falling. In multiple fallers, falls were associated with greater disease activity. Cervical muscle stiffness in AS may cause non-veridical proprioceptive inputs and contribute to increased fall frequency similar to individuals with soft-tissue cervicothoracic pain.

Cochlear nerve deficiency in SOX11-related Coffin-Siris syndrome.

The phenotypic spectrum of SOX11-related Coffin-Siris syndrome (CSS) is expanding with reports of new associations. SOX11 is implicated in neurogenesis and inner ear development. Cochlear nerve deficiency, absence or hypoplasia, is commonly associated with cochlear canal stenosis or with CHARGE syndrome, a monogenic condition that affects inner ear development. SOX11 is a transcription factor essential for neuronal identity, highly correlated with the expression of CHD7, which regulates SOX11. We present two unrelated probands, each with novel de novo SOX11 likely pathogenic variants and phenotypic manifestations of CSS including global developmental delay, growth deficiency, and hypoplastic nails. They have unilateral sensorineural hearing loss due to cochlear nerve deficiency confirmed on MRI. SOX11 is implicated in sensory neuron survival and maturation. It is highly expressed in the developing inner ear. Homozygous ablation of SOX11 in a mouse model resulted in a reduction in sensory neuron survival and decreased axonal growth. A heterozygous knockout mice model had hearing impairment with grossly normal inner ear structures like the two probands reported. We propose cochlear nerve deficiency as a new phenotypic feature of SOX11-related CSS. Magnetic resonance imaging is useful in delineating the cochlear nerve deficiency and other CSS-related brain malformations.

Further delineation of BCAP31-linked intellectual disability: description of 17 new families with LoF and missense variants.

The BCAP31 gene, located at Xq28, encodes BAP31, which plays a role in ER-to-Golgi anterograde transport. To date, BCAP31 pathogenic variants have been reported in 12 male cases from seven families (six loss of function (LoF) and one missense). Patients had severe intellectual disability (ID), dystonia, deafness, and central hypomyelination, delineating a so-called deafness, dystonia and cerebral hypomyelination syndrome (DDCH). Female carriers are mostly asymptomatic but may present with deafness. BCAP31 is flanked by the SLC6A8 and ABCD1 genes. Contiguous deletions of BCAP31 and ABCD1 and/or SLC6A8 have been described in 12 patients. Patients with deletions including BCAP31 and SLC6A8 have the same phenotype as BCAP31 patients. Patients with deletions of BCAP31 and ABCD1 have contiguous ABCD1 and DXS1375E/BCAP31 deletion syndrome (CADDS), and demonstrate a more severe neurological phenotype with cholestatic liver disease and early death. We report 17 novel families, 14 with intragenic BCAP31 variants (LoF and missense) and three with a deletion of BCAP31 and adjacent genes (comprising two CADDS patients, one male and one symptomatic female). Our study confirms the phenotype reported in males with intragenic LoF variants and shows that males with missense variants exhibit a milder phenotype. Most patients with a LoF pathogenic BCAP31 variant have permanent or transient liver enzyme elevation. We further demonstrate that carrier females (n = 10) may have a phenotype comprising LD, ID, and/or deafness. The male with CADDS had a severe neurological phenotype, but no cholestatic liver disease, and the symptomatic female had moderate ID and cholestatic liver disease.

Cervicothoracic Mechanical Impairment as Part of Complete Neurological Fall Risk Appraisal.

BACKGROUND: Assessment of individuals at risk for falling entails comprehensive neurological and vestibular examinations. Chronic limitation in cervical mobility reduces gaze accuracy, potentially impairing navigation through complex visual environments. Additionally, humans with scoliosis have altered otolithic vestibular responses, causing imbalance. We sought to determine whether dynamic cervical mobility restrictions or static cervicothoracic impairments are also fall risk factors. METHODS: We examined 435 patients referred for soft-tissue musculoskeletal complaints; 376 met criteria for inclusion (mean age 52; 266 women). Patients were divided into nonfallers, single fallers, and multiple fallers, less or greater than 65 years old. Subject characteristics, dynamic cervical rotations, and static cervicothoracic axial measurements were compared between groups. Fear of falling was evaluated using the Falls Efficacy Scale-International questionnaire. RESULTS: Long-standing cervicothoracic pain and stiffness conferred increased risk of falling. Neck rotation amplitudes decreased with longer duration musculoskeletal symptoms and were significantly more restricted in fallers, doubling the risk of falling and contributing to increased fear of falling. Mid-thoracic scoliosis amplitudes increased over time, but static axial abnormalities were not greater among fallers, although thoracic kyphoscoliosis heightened fear of falling. CONCLUSION: In patients at fall risk, thoracic kyphoscoliosis and dynamic neck movements should be assessed, in addition to standard vestibular and neurological evaluations. Additionally, patients with soft tissue cervicothoracic pain and restricted mobility have increased fall frequency and fear of falling, independent of other fall risk factors and should undergo complete fall risk appraisal.

Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy. METHODS: SELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts ('non-responders') and at week 26 based on Clinical Disease Activity Index (CDAI) >10 ('incomplete-responders') without washout. RESULTS: A total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups. CONCLUSIONS: These observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

Developing asymmetry in a screening mammogram: A cautionary tale of a missed cancer.

The developing asymmetry has a 12-15% risk of malignancy but poses challenges of detection and interpretation due to the lack of typical features of cancer and the frequent absence of an ultrasound correlate. Failure to biopsy these lesions may lead to delayed diagnosis of breast cancer.

Inaccurate Saccades and Enhanced Vestibulo-Ocular Reflex Suppression during Combined Eye-Head Movements in Patients with Chronic Neck Pain: Possible Implications for Cervical Vertigo.

BACKGROUND: The primate ocular motor system is designed to acquire peripheral targets of interest by coordinating visual, vestibular, and neck muscle activation signals. The vestibulo-ocular reflex (VOR) is greatly reduced at the onset of large eye-head (gaze) saccades and resumes before the end of the saccades to stabilize eye-in-orbit and ensure accurate target acquisition. Previous studies have relied on manipulating head movements in normal individuals to study VOR suppression and gaze kinematics. We sought to determine if reduced head-on-trunk movement alters VOR suppression and gaze accuracy similar to experiments involving normal subjects and if intentionally increasing head and neck movement affects these dynamics. METHODS: We measured head and gaze movements using magnetic search coil oculography in eight patients with cervical soft tissue disorders and seven healthy subjects. All participants made horizontal head-free saccades to acquire a laser dot target that stepped pseudorandomly 30-65° to either side of orbital mid-position, first using typical head and eye movements and again after being instructed to increase head amplitudes as much as possible. RESULTS: Compared to healthy subjects, patients made smaller head movements that contributed only 6% to total gaze saccade amplitudes. Head movements were also slowed, prolonged, and delayed. VOR suppression was increased and prolonged. Gaze saccades were inaccurate and delayed with long durations and decreased peak velocities. CONCLUSION: In patients with chronic neck pain, the internal commands issued for combined eye-head movements have large enough amplitudes to create accurate gaze saccades; however, because of increased neck stiffness and viscosity, the head movements produced are smaller, slower, longer, and more delayed than they should be. VOR suppression is disproportionate to the size of the actual gaze saccades because sensory feedback signals from neck proprioceptors are non-veridical, likely due to prolonged coactivation of cervical muscles. The outcome of these changes in eye-head kinematics is head-on-trunk stability at the expense of gaze accuracy. In the absence of vestibular loss, the practical consequences may be dizziness (cervical vertigo) in the short term and imbalance and falls in the long term.

Radiographic skeletal survey for non-accidental injury: systematic review and development of a national New Zealand protocol.

INTRODUCTION: Clinically occult fractures from non-accidental injury (NAI) are best detected on radiographic skeletal survey. However, there are regional variations regarding the views included in such surveys. We undertook a systematic review of the evidence supporting skeletal survey protocols to design a protocol that could be implemented across New Zealand. METHODS: In June 2013, we searched Medline, Google Scholar, the Cochrane database, UpToDate and relevant reference lists for English-language publications on skeletal survey in NAI from 1946. We included publications that contained a protocol or reported evidence supporting including, or excluding, specific views in a skeletal survey. All included publications were critically appraised. Based on this systematic review, a draft protocol was developed and presented to an Australian and New Zealand Society for Paediatric Radiology NAI symposium in October 2013. Feedback from the symposium and later discussions was incorporated into the final protocol. RESULTS: We identified 2 guidelines for skeletal survey, 13 other protocols and 15 articles providing evidence for inclusion of specific images in a skeletal survey. The guidelines scored poorly on critical appraisal of several aspects of their methods. We found no studies that validate any of the protocols or compare their performance. Evidence supporting inclusion in a skeletal survey is limited to ribs, spine, pelvis, hands and feet, and long bone views. Our final protocol is a standardised, two-tiered protocol consisting of between 17 and 22 views. CONCLUSION: A standardised protocol for radiographic skeletal survey protocol has been developed in New Zealand. We present it here for consideration by others.

The Spondyloarthritis Research Consortium of Canada registry for spondyloarthritis.

The Spondyloarthritis Research Consortium of Cananda (SPARCC) is a transdiscliplinary research network of investigators interested in spondyloarthritis. The group has been supported by a new research initiative by The Arthritis Society. SPARCC aims to address the genetic basis of susceptibility of the disease and develop and validate clinical and imaging outcomes to assess disease activity and structural damage over time, the response to therapy, and the clinical burden of illness in terms of quality of life and disability. The first step was to develop a database that would allow ascertainment of phenotype for genetic studies, as well as accurate and detailed longitudinal information for disease expression and outcome studies. This article describes the SPARCC database and outlines difficulties and possible solutions for maintaining such a database.

Beneficial effects of adalimumab on biomarkers reflecting structural damage in patients with ankylosing spondylitis.

OBJECTIVE: We analyzed the effects of adalimumab on biomarkers predictive of structural damage in inflammatory arthritis. METHODS: In a 24-week randomized controlled trial, patients with active ankylosing spondylitis (AS) received adalimumab 40 mg or placebo every other week. Efficacy measures included ASsessment in Ankylosing Spondylitis International Working Group response, Bath AS Disease Activity Index (BASDAI), Total Back Pain, Bath AS Functional Index, C-reactive protein (CRP), and patient's global assessment of disease activity. Urinary type II collagen C-telopeptides (CTX-II), serum type I collagen N-telopeptides (NTX), and serum metalloproteinase-3 (MMP-3) were assessed using ELISA for treatment-group differences at baseline, 12, and 24 weeks. We determined correlations between changes in biomarkers and AS efficacy outcomes. RESULTS: A total of 82 patients (38 adalimumab, 44 placebo) enrolled. At 12 and 24 weeks, significant reductions in urinary CTX-II and MMP-3, but not NTX concentrations, were observed for adalimumab versus placebo (p<0.001). Significant baseline correlations were noted between CRP and CTX-II (r=0.71), MMP-3 (r=0.45), and NTX (r=0.37) (p

Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS). METHODS: This was a randomized, multicenter, double-blind, placebo-controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24-week double-blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. RESULTS: The spine SPARCC score in placebo-treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab-treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo-treated patients and by 52.9% in adalimumab-treated patients (P = 0.017). The response in adalimumab-treated patients was maintained at week 52. Placebo-treated patients were switched to open-label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab-treated patients, a reduced C-reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018). CONCLUSION: Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 weeks.

The Canadian Rheumatology Association/ Spondyloarthritis Research Consortium of Canada treatment recommendations for the management of spondyloarthritis: a national multidisciplinary stakeholder project.

OBJECTIVE: Development of treatment recommendations for arthritis has traditionally relied on the compilation of evidence-based data by experts in the field despite recommendations by various bodies for broad stakeholder input. Our objectives were: (1) To develop evidence-based treatment recommendations for the management of spondyloarthritis (SpA) in Canada that also incorporate the perspective of multiple stakeholders. (2) To generate a procedural template for the multidisciplinary development of treatment recommendations. METHODS: The process was directed by a steering committee comprising the SPARCC Executive, rheumatologists from academic and community-based practice, patient consumers, and a representative from the John Dossetor Health Ethics Centre. Guidelines established by EULAR and stipulated in the AGREE instrument were followed. First, a working document was drafted that included a referenced summary of the evidence-based data and the 12 national arthritis care standards developed by the Alliance for the Canadian Arthritis Program. Second, a Web-based survey was conducted among patient consumers to address the relevance to patients of 2 primary outcome instruments that assess the effectiveness of treatment. Third, a list of questions was generated for drafting propositions by the ethics consultant. A Delphi consensus exercise was then conducted. RESULTS: Consensus was generated on a final list of 38 treatment recommendations categorized under the subject headings of general management principles, ethical considerations, target groups, definition of target disease, disease monitoring, and specific management recommendations. CONCLUSION: Using broad stakeholder input, we provide treatment recommendations to guide clinical practice and access to care for patients with SpA in Canada.

Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy.

OBJECTIVE: To demonstrate the safety and efficacy of adalimumab for the treatment of active psoriatic arthritis (PsA) in patients with an inadequate response to disease modifying antirheumatic drugs (DMARD). METHODS: In a placebo controlled, double-blind, randomized, multicenter study, patients were treated for 12 weeks with subcutaneous injections of adalimumab 40 mg every other week (eow) or placebo, followed by a period of open-label treatment with adalimumab 40 mg eow. The primary efficacy endpoint was the percentage of patients who met the American College of Rheumatology (ACR20) core criteria at Week 12. Secondary efficacy measures included the modified Psoriatic Arthritis Response Criteria (PsARC) and assessments of disability, psoriatic lesions, and quality of life. For missing data, nonresponder imputation was used for ACR and PsARC scores and last observation carried forward for other measures. RESULTS: A total of 100 patients received study drug (51 adalimumab, 49 placebo). At Week 12, an ACR20 response was achieved by 39% of adalimumab patients versus 16% of placebo patients (p = 0.012), and a PsARC response was achieved by 51% with adalimumab versus 24% with placebo (p = 0.007). At Week 12, measures of skin lesions and disability were statistically significantly improved with adalimumab. After Week 12, open-label adalimumab provided continued improvement for adalimumab patients and initiated rapid improvement for placebo patients, with ACR20 response rates of 65% and 57%, respectively, observed at Week 24. Serious adverse events had similar frequencies during therapy with placebo (4.1%), blinded adalimumab (2.0%), and open-label adalimumab (3.1%). No serious infections occurred during adalimumab therapy. CONCLUSION: In this study of patients who had active PsA and a previous, inadequate response to DMARD therapy, adalimumab was well tolerated and significantly reduced the signs, symptoms, and disability of PsA during 12 weeks of blinded and 12 weeks of open-label therapy. Adalimumab also improved psoriasis in these patients.

Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates.

We describe 7 Polynesian babies with a unique severe form of holocarboxylase synthetase deficiency characterized by antenatal growth retardation, subependymal cysts, only partial response to biotin, and a poor outcome.

Encouraging physician appropriate prescribing of non-steroidal anti-inflammatory therapies: protocol of a randomized controlled trial [ISRCTN43532635].

BACKGROUND: Traditional non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used class of therapy in the treatment of chronic pain and inflammation. The drugs are effective and can be relatively inexpensive thanks to available generic versions. Unfortunately the traditional NSAIDs are associated with gastrointestinal complications in a small proportion of patients, requiring costly co-therapy with gastro-protective agents. Recently, a new class of non-steroidal anti-inflammatory agents known as coxibs has become available, fashioned to be safer than the traditional NSAIDs but priced considerably higher than the traditional generics. To help physicians choose appropriately and cost-effectively from the expanded number of anti-inflammatory therapies, scientific bodies have issued clinical practice guidelines and third party payers have published restricted reimbursement policies. The objective of this study is to determine whether an educational intervention can prompt physicians to adjust their prescribing in accordance with these expert recommendations. METHODS: This is an ongoing, randomized controlled trial. All primary care physicians in Manitoba, Canada have been randomly assigned to a control group or an intervention study group. The educational intervention being evaluated consists of an audit and feedback mechanism combined with optional participation in a Continuing Medical Education interactive workshop. The primary outcome of the study is the change, from pre-to post-intervention, in physicians' appropriate prescribing of non-steroidal anti-inflammatory therapies for patients requiring chronic treatment. Three classes of non-steroidal anti-inflammatory therapies have been identified: coxib therapy, traditional NSAID monotherapy, and traditional NSAID therapy combined with gastro-protective agents. Appropriate prescribing is defined based on international clinical practice guidelines and the provincial drug reimbursement policy in Manitoba.

High-throughput single-nucleotide polymorphism analysis of the IL1RN locus in patients with ankylosing spondylitis by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.

OBJECTIVE: To examine single-nucleotide polymorphisms (SNPs) in the 3' region of the IL1RN gene in a large Caucasoid case-control series and in ankylosing spondylitis (AS) families from Western Canada by use of high-throughput MassArray matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry SNP typing. METHODS: An association analysis was performed in a case-control cohort of 394 AS cases and 500 controls. Family-based association analysis was performed in 58 simplex and 13 multiplex families. Three SNPs located in the 3' region of the IL1RN gene (T/C at position 27810 in exon 4, T/C at position 30735 in exon 6, and G/C at position 31017 in exon 6) were examined by high-throughput MassArray MALDI-TOF mass spectrometry. Haplotype inference software programs were used to infer the most likely haplotypes and to compare haplotype frequencies, which were then further analyzed in family-based association studies by transmission disequilibrium tests. RESULTS: The frequency of allele C at SNP position 30735 in exon 6 was significantly increased in AS cases (35.1%) versus controls (27.8%), as was the phenotype frequency (61.7% versus 48.6%). A significantly increased frequency of SNP allele G at position 31017 in exon 6 in cases (32.9%) versus controls (28.3%) was also noted. A highly significant difference in the overall distribution of haplotype frequencies was evident between cases and controls, with significant increases in the frequencies of the 27810C/30735C/31017C and 27810C/30735T/31017G haplotypes, but a significant reduction in the estimated frequency of the 27810C/30735T/31017C haplotype, in the AS cases. Estimation of haplotype frequencies based on 2 SNP markers indicated a highly significant increase in the 30735C/31017C haplotype and a highly significant decrease in the 30735T/31017C haplotype in cases compared with controls. Preliminary evidence for reduced transmission of the 27810C/30735T/31017C 3-marker haplotype was also found in family-based association analyses. CONCLUSION: Our data establish a highly significant disease association with markers in the IL1RN gene. In the absence of nonsynonymous coding sequence substitutions, it is possible that the primary disease-associated locus regulates gene expression. Association with specific haplotypes raises the possibility that the primary disease locus is in linkage disequilibrium with a specific combination(s) of markers in the IL1RN gene.

Canadian Rheumatology Association Consensus on the use of anti-tumor necrosis factor-alpha directed therapies in the treatment of spondyloarthritis.

Spondyloarthritis (SpA) represents a group of related arthritides characterized by their association with HLA-B27 and the development of sacroiliitis and enthesitis. Functional impairment, disability, and loss of quality of life may resemble that observed in rheumatoid arthritis. The SpA Research Consortium of Canada (SPARCC) is an informal association of rheumatologist members of the Canadian Rheumatology Association (CRA) with a special interest in therapeutics and outcomes research in SpA. Recent experience with anti-tumor necrosis factor-a (anti-TNF-a) directed therapies prompted a consensus-based evaluation of the evidence supporting their efficacy, safety, and appropriate use in SpA. We evaluated the clinical evidence in support of anti-TNF-a directed therapies in SpA. Medline was searched using appropriate keywords. Abstracts of the 1999-2002 annual meetings of the American College of Rheumatology and the European Congress of Rheumatology were extracted and admitted if sufficient detail was available to determine the level of evidence. Recommendations were based on randomized placebo-controlled trials (Level A evidence) and clinical studies without randomization (Level B evidence). Where the scientific literature was incomplete, recommendations reflected the consensus of SPARCC members (Level C evidence). Following development of an original draft document, consensus for revisions was achieved among members of SPARCC. The document was then posted on the CRA website prior to its final revision. The following recommendations have been endorsed by the Therapeutics Committee of the CRA: Infliximab and etanercept are indicated for reduction of signs and symptoms of moderate to severely active SpA in patients who have had an inadequate response to maximal doses of > or = 2 nonsteroidal antiinflammatory drugs (NSAID) over a 3-month period of observation; and either sulfasalazine or methotrexate is indicated in those with predominantly active peripheral arthritis. Current evidence supports their use as monotherapy (level of evidence A) for at least one year. NSAID and/or second line therapy with either sulfasalazine or methotrexate can be continued concomitantly. There is no evidence addressing potential advantages or disadvantages of combining methotrexate with anti-TNF therapy for SpA. Recommended doses for adults are: infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter; etanercept 25 mg subcutaneously twice weekly. No therapy has been shown to slow progression of axial disease in SpA, and prognostic factors for determining response to therapy remain to be determined. It is the position of the CRA that all therapeutic options should be equally available according to the best judgments of the treating physician and the informed decision of the patient.