PROGNOSIS, COURSE OF DISEASE, AND TREATMENT OF THE SPONDYLOARTHROPATHIES

Rheumatoid arthritis (RA) can have various infectious mimics. As immunosuppressive agents used in treatment can aggravate the underlying infections, correct diagnosis of RA and ruling out infections is important. Numerous viral infections (Parvovirus B19, Hepatitis B, Hepatitis C, Chikungunya and other alphaviruses, human immunodeficiency virus (HIV) and various other viruses), mycobacterial infections (Poncet's disease, tubercular septic arthritis, and leprosy), bacterial arthritis, brucellosis and Lyme disease are among common infections that mimic RA. Widespread travel and tourism, especially to exotic areas, high risk sexual behavior and widespread use of immunosuppressive and chemotherapeutic agents has led to numerous outbreaks of infections in areas where these infections were never reported before. Hence, rheumatologists all over the world should be familiar with musculoskeletal manifestations of infections. History of travel, comorbid fever, skin rash, genital ulcers, urethral discharge, the consumption of unpasteurized milk, lymphadenopathy, tenosynovitis, low platelet count, and positive Mantoux test can offer potential diagnostic clues. Serological testing, cultures, specific radiological signs and deoxyribonucleic Acid (DNA) amplification techniques often aid in diagnosis. Treatment mainly consists of antimicrobial agents, analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). However, immunosuppressive agents including steroids and disease modifying anti-rheumatic drugs (DMARDs) are needed occasionally in different refractory and prolonged illnesses. Most of the times, episodes of arthritis are self-limiting and respond to treatment of underlying cause. However, few infections like Chikungunya and Lyme's disease can lead to chronic arthritis as well.

Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin 17A, has shown significant and sustained improvement in the signs and symptoms of ankylosing spondylitis over 3 years in the MEASURE 2 study. We report the 5-year (end-of-study) results of subcutaneous secukinumab 150 mg in the MEASURE 2 study.

MEASURE 2 was a phase 3, double-blind, randomised, placebo-controlled, study done in 13 countries and 53 centres. Patients with ankylosing spondylitis who were 18 years of age or older and fulfilled the modified New York criteria were randomly assigned to receive secukinumab (150 mg or 75 mg) or placebo subcutaneously at baseline and weeks 1, 2, and 3, and then every 4 weeks from week 4. At week 16, patients initially given placebo were randomly assigned again (placebo switchers) to receive secukinumab 150 mg or 75 mg. Efficacy results are reported for patients initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at week 16. An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning week 140. We assessed efficacy endpoints at week 260 (5 years), including Assessment of Spondyloarthritis International Society (ASAS) 20 and ASAS 40, inactive disease according to ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, Short Form-36 Physical Component Summary, and ASAS partial remission. Analyses were stratified by anti-tumour necrosis factor (TNF) status (anti-TNF-naive and anti-TNF inadequate response). The safety analysis included all patients who received one dose or more of secukinumab. We report data as observed without accounting for missing data. The MEASURE 2 study was registered with ClinicalTrials.gov, NCT01649375.

219 patients were randomly assigned during the trial and 150 (68%) completed 5 years of treatment, including 82 (77%) of 106 patients in the secukinumab 150 mg group and 68 (65%) of 105 in the secukinumab 75 mg group. Efficacy analysis in the secukinumab 150 mg group included 53 patients who completed the study and one additional patient who was assessed in the treatment period weeks 212–260, but did not complete the study. 134 (61%) of 219 patients were anti-TNF-naive and 85 (39%) were anti-TNF inadequate responders. ASAS responses at 5 years with secukinumab 150 mg were 36 (67%) of 54 patients (ASA20) and 27 (50%) patients (ASAS40). Sustained improvement was observed across other efficacy endpoints with secukinumab 150 mg at 5 years. At 5 years, the proportion of patients achieving efficacy endpoints of BASDAI 50 response was 53% (44/83); ASAS 5/6 response was 51% (42/83); ASDAS-CRP inactive disease was 21% (17/81); and ASAS partial remission was 25% (21/83). Exposure-adjusted incidence rates with any secukinumab dose for selected adverse events were 1·0 per 100 patient-years (95% CI 0·4–1·9) for Candida infections, 0·5 (0·1–1·2) for Crohn's disease, 0·4 (0·1–1·1) for ulcerative colitis, 0·6 (0·2–1·4) for major adverse cardiovascular events, 0·5 (0·1–1·2) for uveitis, and 0·6 (0·2–1·4) for malignant or unspecified tumours.

Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in patients with ankylosing spondylitis after 5 years of treatment. The safety profile of secukinumab remained consistent with previous reports.

Novartis Pharma.

The spondyloarthritis (SpA) diseases comprise different diseases, which share similar genetic risk factors and similar clinical symptoms, such as inflammatory back pain or asymmetric peripheral arthritis. Ankylosing spondylitis (AS), the prototypic form of SpA, is characterized by axial inflammation and new bone formation.

HLA-B27 is the most relevant genetic risk factor, apart from several non-MHC genes. The mechanism of how HLA-B27 promotes disease development is still unclear. One hypothesis claims that HLA-B27 generates arthritogenic peptides, while other hypotheses propose that the disease development is related to the predisposition of HLA-B27 to misfold.

Bacteria are known triggers of reactive arthritis and gut bacteria are suspected to be involved in AS pathology. However, as bacterial antigens have not been detected at axial sites, the target of infiltrating T cells is still unclear. Proinflammatory cytokines, such as tumor necrosis factor alpha (TNFα) are highly expressed within the inflamed tissue and TNFα inhibitors are very effective in clearing inflammation.

L’arthrite réactionnelle complique parfois les infections digestives à certains bacilles Gram négatifs, tels que Salmonella, Yersinia, Shigella et Campylobacter. De manière moins fréquente, des arthrites inflammatoires ont également été décrites suivant une infection par Clostridium difficile. Les mécanismes moléculaires de la maladie et notamment le rôle du HLA-B27 ont été précisés ces dernières années. Cependant, peu d’études ont spécifiquement évalué l’efficacité des traitements de fonds et c’est pourquoi les stratégies thérapeutiques sont grandement calquées sur celles des autres spondyloarthrites. L’objectivation de la persistance des bactéries et la dissémination de signaux de danger avaient initialement fourni un rationnel à l’emploi d’antibiothérapie, avec des résultats contradictoires selon les études. Nous reviendrons sur les hypothèses physiopathologiques ainsi que la prise en charge thérapeutique de ces arthrites réactionnelles, en s’appuyant sur les données de la littérature.

Intestinal infection by Gram-negative pathogens, such as Salmonella, Yersinia, Shigella and Campylobacter, is sometimes complicated by reactive arthritis. Inflammatory arthritis secondary to infection by Clostridium difficile has also been described, but less frequently. There have been recent insights over the past few years regarding the molecular mechanisms underlying reactive arthritis, including the role of HLA-B27. However, few studies have focused on the efficacy of treatments and thus current treatment strategies are similar to the ones used for other spondyloarthritides. Bacteria persistence and systemic presence of danger signals had initially warranted the use of antibiotics after the resolution of the intestinal infection, but with discordant results. We will review the principal physiopathological mechanisms and treatment strategies of these reactive arthritides, currently detailed in the literature.

Il existe un chevauchement bien connu entre spondyloarthrites (SpA) et maladies inflammatoires chroniques de l’intestin (MICI). Une inflammation intestinale microscopique est présente chez près de la moitié des patients avec SpA ; elle peut évoluer vers une MICI, en particulier en cas d’inflammation chronique. De façon étonnante, ces patients semblent avoir un œdème médullaire osseux plus prononcé à l’IRM des articulations sacro-iliaques, et une évolution clinique moins favorable, ce qui pourrait avoir des conséquences thérapeutiques notables. Au surplus, un tiers des patients porteurs d’une MICI ont des signes d’inflammation articulaire ou des lombalgies inflammatoires. Cependant, cela n’a pas été évalué de façon systématique, en particulier en termes d’études IRM des articulations sacro-iliaques. Cette mise au point fournit une revue des données cliniques les plus récentes sur le chevauchement entre inflammation intestinale et inflammation articulaire.

There is a well-known overlap between spondyloarthritis (SpA) and inflammatory bowel disease (IBD). Microscopic gut inflammation is present in up to half of all SpA patients and can evolve into IBD, especially in case of the chronic type of inflammation. Interestingly, these patients seem to have more pronounced bone marrow edema on MRI of the sacroiliac joints (SIJ) and a less favorable disease course, which could have important therapeutic consequences. Moreover, a third of patients with IBD show signs of joint inflammation or inflammatory back pain. However, this has not been studied in a systematic way, especially in terms of studies with MRI of the SIJ. This review provides an overview of the most recent clinical insights on the overlap between gut and joint inflammation.

The aim of this study was to find out if reactive arthritis was involved in the aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking for bacterial antigens in the synovial membrane of the TMJ, and by studying the antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients with chronic closed lock. Patients with reciprocal clicking and healthy subjects acted as controls. We studied a total of 43 consecutive patients, 15 with chronic closed lock, 13 with reciprocal clicking, and 15 healthy controls with no internal derangements of the TMJ. Venous blood samples were collected from all subjects for measurement of concentrations of HLA tissue antigen and serology against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp., Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from patients with closed lock and reciprocal clicking were obtained during discectomy and divided into two pieces, the first of which was tested by strand displacement amplification for the presence of C trachomatis, and the second of which was analysed for the presence of species-specific bacterial DNA using 16s rRNA pan-polymerase chain reaction (PCR). There were no significant differences between the groups in the incidence of antibodies against M pneumoniae, Salmonella spp. or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni. We found no bacterial DNA in the synovial fluid from any patient. The HLA B27 antigen was present in 2/15 subjects in both the closed lock and control groups, and none in the reciprocal clicking group. In conclusion, reactive arthritis does not seem to be the mechanism of internal derangement of the TMJ.