Current therapeutics for spondyloarthritis

INTRODUCTION: Ankylosing spondylitis (AS) belongs to a clinically related group of disorders named spondyloarthritis (SpA) that mainly affect the axial skeleton and present with specific extra-articular manifestations. The therapeutic management of AS and other SpA has considerably progressed over the past 10 years. AREAS COVERED: This paper provides a review of the available treatments for AS including traditional treatments (NSAIDs, sulfasalazine and methotrexate, local corticosteroids) and biological therapies (TNF-α antagonists), as well as nonpharmacological procedures (education and physical therapy) and specific recommendations for this therapeutic management. EXPERT OPINION: NSAIDs remain the first-line treatment in patients with AS, especially with axial disease. There is an increasing amount of evidence showing the short-term and long-term efficacy of TNF-α antagonists in AS, with the control of pain, extra-articular manifestations and spinal inflammation as evidenced by MRI. By contrast, there is no proof for the control of radiographic progression at the spine with these agents. An early diagnosis is now possible using the new classification criteria for SpA. However, it remains to be established if an early intervention might control the progression of the disease. Since about 20 - 25% of patients are considered as nonmajor responders to TNF-α blockers, there is an unmet need for developing new biological therapies. Targeting the IL-17 pathway may be an interesting option. International recommendations for the management of AS by the Assessment of Spondyloarthritis (ASAS) group were recently updated and discussed the respective place of each current therapeutic option in AS.     

Therapeutic advances in ankylosing spondylitis

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. This condition is responsible for back pain, stiffness, but also loss of functional capacity with socio-economic consequences. The management of AS includes patient education, rest, a programme of regular physical exercise, together with the use of NSAIDs. Second-line treatments are required in cases of severe or refractory AS, however only sulfasalazine has proven to benefit AS patients with peripheral arthritis. In spite of this management, the disease may not be adequately controlled, mainly for patients with refractory axial disease, enthesopathy or extra-articular features. Thus, new innovative treatments are needed for AS. It is likely that the new NSAIDs or COX-2 specific inhibitors will certainly take the place of the conventional NSAIDs, with regard to their superior tolerability. Methotrexate is a therapeutic option for AS treatment, but its usefulness in this disease remains to be established in adequate controlled studies. Finally, the TNF-α targeting drugs, namely thalidomide and the anti-TNF-α mAb, infliximab, have given promising results in the treatment of severe and/or refractory AS patients, however further controlled studies are required. In addition, the long-term use (efficacy and tolerability) of these two agents deserves attention.     

New treatment options and emerging drugs for axial spondyloarthritis: biological and targeted synthetic agents

Introduction: Ankylosing spondylitis (AS) and axial spondyloarthritis (ax SpA) are chronic inflammatory diseases mainly involving the axial skeleton. Pharmacological treatments for AS and ax SpA usually include local glucocorticoid injections, NSAIDs and anti-TNFα agents. Since around 30% to 40% of patients are non responders or intolerant to anti-TNFα agents, we need new therapeutic options for AS and ax SpA.

Areas covered: This review describes the new biological agents that can be used or are in development for AS or ax SpA as well as emerging synthetic targeted drugs.

Expert opinion: Based on the rationale of the involvement of the IL-23/Th17 axis in AS, novel biological agents have been developed and include secukinumab, an anti-IL-17A agent and ustekinumab, an anti-IL-23 antibody. New compounds in the class of synthetic drugs are apremilast, a PDE4 inhibitor, and inhibitors of kinase pathways. Secukinumab gave positive results in the treatment of AS. Ustekinumab yielded promising results in AS in an open labeled study. Apremilast is not effective in AS while results with kinase inhibitors are preliminary. Future studies will clarify the place of secukinumab in the therapeutic management of AS, its influence on radiographic progression and its effects on the non radiographic form of the disease.     

Pharmacological management of axial spondyloarthritis in adults

ABSTRACT

Introduction: Spondyloarthritis (SpA) refers to a group of disorders sharing common clinical, genetic and imaging characteristics. Axial (ax) SpA corresponds to a subgroup that mainly affects the axial skeleton, leading to inflammatory back pain and progressive radiographic changes of the sacroiliac joints and the spine. axSpA are currently subdivided into two forms, namely the radiographic and nonradiographic form, and are associated with musculoskeletal pain, restriction of spinal mobility, specific extra-articular features and overall, altered quality of life. The therapeutic management of axSpA has considerably progressed and is now well standardized.

Areas covered: Herein, the author reviews the pharmacological treatments that may be used in axSpA, including radiographic and nonradiographic forms in addition to the role of nonsteroidal anti-inflammatory drugs (NSAIDs), TNF alpha (TNFi), and IL-17A (IL-17Ai) inhibitors.

Expert opinion: NSAIDs remain the mainstay of initial therapy and biological agents may be then envisaged. TNFi and IL-17Ai may be used in axSpA, but physicians have more experience with TNFi. Only TNFi are licensed for the treatment of nonradiographic axSpA. IL-17Ai may be used as first or second line biologic disease modifying antirheumatic drugs (bDMARDs) and further results are needed to better define their position in the therapeutic management of axSpA.     

Current use of biologicals for the treatment of spondyloarthropathies

Spondyloarthropathies (SpA) are a group of related disorders. The hallmark symptoms include spondylitis, pauci-articular synovitis and enthesiopathy. In an important number of cases, subclinical gut inflammation with pathological findings resembling Crohn’s disease can be found. Some of these patients may eventually develop overt Crohn’s disease. Conventional medical therapy in patients with SpA consists of non-steroidal anti-inflammatory drugs (NSAIDs). Sulphasalazin can be co-administered, especially in cases of chronic synovitis or enthesiopathy. Recently, experience with anti-TNF-α monoclonal antibodies (infliximab), a new class of biological compounds, has opened new avenues for treating patients with SpA. In particular, infliximab used in two open studies gave significant benefit on the locomotor manifestations in patients with Crohn’s disease, in patients with ankylosing spondylitis, undifferentiated SpA and psoriatic arthritis. Etanercept, another TNF-α antagonist (soluble receptor), was shown to induce benefit in a placebo-controlled study in patients with psoriatic arthritis. The relationship between SpA and inflammatory bowel disease lead to the hypothesis that interfering with gut inflammation in patients with SpA would yield a potential target for modulating the synovitis in these patients. Thus, besides TNF-α blockade, other strategies with potential efficacy can be envisioned, such as IL-10, ICAM-1 antisense or anti-₄β₇ antibodies.     

Therapeutic advances in ankylosing spondylitis

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. This condition is responsible for back pain, stiffness, but also loss of functional capacity with socio-economic consequences. The management of AS includes patient education, rest, a programme of regular physical exercise, together with the use of NSAIDs. Second-line treatments are required in cases of severe or refractory AS, however only sulfasalazine has proven to benefit AS patients with peripheral arthritis. In spite of this management, the disease may not be adequately controlled, mainly for patients with refractory axial disease, enthesopathy or extra-articular features. Thus, new innovative treatments are needed for AS. It is likely that the new NSAIDs or COX-2 specific inhibitors will certainly take the place of the conventional NSAIDs, with regard to their superior tolerability. Methotrexate is a therapeutic option for AS treatment, but its usefulness in this disease remains to be established in adequate controlled studies. Finally, the TNF-alpha targeting drugs, namely thalidomide and the anti-TNF-alpha mAb, infliximab, have given promising results in the treatment of severe and/or refractory AS patients, however further controlled studies are required. In addition, the long-term use (efficacy and tolerability) of these two agents deserves attention.     

Impact of biological therapy on spondyloarthritis

Purpose

In this review, we focus on the clinical and radiological aspects related to the biological therapy of ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and psoriatic arthritis (PsA).

Methods

A review was carried out in the main medical databases to evaluate the available literature.

Results

Even if there is emerging interest for the role of biological agents other than tumour necrosis factor (TNF)-α inhibitors in spondyloarthritis, anti-TNF-α treatment is currently the only effective therapy for patients in whom conventional therapy with non-steroideal anti-inflammatory drugs (NSAIDs) has failed. Nevertheless, the potential impact of earlier treatment and the best drugs or combinations of drugs for preventing radiographic progression in SpA are yet to be determined.

Conclusions

Anti-TNF-α treatment is currently used with efficacy in the greater part of patients with SpA. In these patients, availability of biological treatment is limited on the bases of potential toxicity and cost. On the basis of clinical trials, biologics other than TNF-α inhibitors can currently not be recommended for the treatment of SpA.     

Evaluation of circulating levels of inflammatory and bone formation markers in axial spondyloarthritis

Studies have demonstrated the important role of bone remodelling and osteoimmunology in the progression of inflammatory lesions in axial spondyloarthritis (SpA) disease. This study was conducted to evaluate the inflammatory response by analysis of the serum levels of pro-inflammatory and new bone formation markers in patients with axial SpA who were treated or not treated with anti-tumour necrosis factor-α (anti-TNF-α) or non-steroidal drugs (NSAIDs) and to identify whether these drugs modify the activity and severity of the disease. The serum levels of myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NO_x), bone alkaline phosphatase (BAP), Dickkopf-1 (DKK-1), and osteoprotegerin (OP) were measured in 52 SpA patients who were treated or not with anti-TNF-α or NSAIDs and in 26 healthy controls using colourimetric and enzyme immunoassay tests. The activity and the severity of illness in patients with SpA were assessed using questionnaires (Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). A significant difference between the controls and the patients without medication was observed in relation to NO_x, BAP, and OP (p < 0.01). When the patients were compared with regard to their treatment, there were no clinically significant differences between the groups (p > 0.05). In conclusion, The NOx, BAP, and OP are emerging as important inflammatory pathways in axial SpA. Also the anti-TNF-α or non-steroidal drugs reduce the inflammation and destructions, however these treatments do not modify the serum levels of these biomarkers.     

Structure-modifying capacity of anti-tumour necrosis factor-alpha therapy in ankylosing spondylitis

Spondylarthropathies (SpA) present mainly with spondylitis, pauciarticular peripheral arthritis and enthesopathy. Ankylosing spondylitis (AS) is the prototype disease in this concept. Other entities include reactive arthritis, arthritis in patients with inflammatory bowel disease, some forms of psoriatic arthritis and undifferentiated SpA. NSAIDs are the classical cornerstone of medical therapy in patients with SpA. The effect of these drugs on disease progression, more specifically the ankylosis, is uncertain. Sulfasalazine can be combined with NSAIDs, particularly if peripheral arthritis symptoms persist. However, this combination therapy is not effective for the spondylitis symptoms. Indeed, AS is one of the rheumatic diseases for which no real disease-modifying antirheumatic treatment is available. Challenges in chronic autoimmune arthritis have changed dramatically, especially since biotechnological compounds became available. These compounds allow for a specific intervention in the immune cascade underlying the disease. Tumour necrosis factor (TNF)-alpha antagonists (monoclonal antibodies such as infliximab, or soluble receptors such as etanercept) are the first representative drugs in this category. Open-label studies have shown the efficacy of these new targeted drugs, which has been confirmed by controlled studies, at least in the short term. Improvements in several clinical parameters, function, quality of life, biological parameters, histopathological synovial characteristics and magnetic resonance imaging, have all been observed. As a result of these favourable results, anti-TNFalpha therapy has been approved for the treatment of AS and should be considered for patients with severe axial symptoms and elevated serological markers of inflammatory activity who have responded inadequately to conventional nonsteroidal therapy. There is evidence that this new therapeutic approach has a disease- and even structure-modifying effect in SpA. In this context, structure modification should not only be seen as inhibition of bone and cartilage destruction but more broadly as modulation of tissue histology. Some questions remain unanswered, such as the long-term efficacy and safety of anti-TNFalpha therapy, the extent of structural benefit and the cost effectiveness. However, despite these concerns, anti-TNFalpha therapy represents a major therapeutic advancement in the treatment of AS.     

Autoimmunity in intervertebral disc herniation: from bench to bedside

Introduction: The cause of low back pain and the pathophysiology of lumbar pain and sciatica have recently been reconsidered basing on current knowledge on cellular and molecular mediators of inflammation. Several cytokines have been considered as potential therapeutic targets to contrast sciatica in patients with disc herniation, and supportive studies suggest a leading role of TNF-α in this contest: therefore, clinical trials have tested TNF-α inhibitors in the clinical setting of the patient with radicular pain secondary to an herniated disc.

Areas covered: The current review deals with the autoimmune theory of disc herniation and its role in determining radiculopathy and neuropathic pain. It also reports the recent evidences that led to the introduction of anti-TNF-α drugs into the clinical setting as a biological therapy for radiculopathy and disc herniation.

Expert opinion: Targeting the TNF-α pathway has demonstrated controversial effects in the tested study population and available results only report a short-term follow-up. More confirmatory studies in terms of long-term clinical results, complications, more effective route of administration and cost-effective analysis are required to establish the real role of this biological therapy in the treatment of patients with disc herniation and neuropathy.     

Emerging drugs for psoriatic arthritis

Importance of the field: The socioeconomic burden of psoriatic arthritis (PsA) is considerable and not different from that of rheumatoid arthritis. Current treatment options do not always allow reaching the therapeutic objectives consisting of the remission of symptoms and prevention of the appearance of damage in the early stage of PsA or the blocking of PsA progression in the established cases.

Areas covered in this review: After reviewing the current treatment choices, we examine the new drugs in clinical Phase II and III trials for PsA up to January 2010. Information was mainly obtained from the network of international clinical trial registries.

What the reader will gain: The current management of PsA includes NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α blocking agents. These last drugs are more effective than traditional DMARDs on symptoms/signs of inflammation, quality of life and function and can inhibit the progression of the structural joint damage. Recent advancement in the knowledge of the immunopathogenesis of PsA has permitted the development of novel drugs including new TNF-α blockers, IL-1, -6, -12, -23 and -17 inhibitors, co-stimulator modulation inhibitors, B-cell depleting agents, small molecules and receptor activator of NF-κB/receptor activator of NF-κB ligand inhibitors.

Take home message: The currently available anti-TNF-α blocking agents have revolutionized the management of PsA. However, there is a need for more effective and safer drugs.     

Bisphosphonates as anti-inflammatory agents in ankylosing spondylitis and spondylarthropathies

NSAIDs remain the cornerstone of the treatment of ankylosing spondylitis (AS) and spondylarthropathies (SpA), and have been successfully used for a long time in these diseases. However, some patients remain refractory or intolerant to NSAIDs and new effective treatments have recently emerged, namely TNF-alpha-blocker agents. Other therapeutic options targeting the bone, such as bisphosphonates, have also been tried in refractory AS or SpA patients. The anti-inflammatory properties of bisphosphonates give the rationale for the use of these compounds in AS and SpA, and include the inhibition of antigen presenting cells, the modulation of pro-inflammatory cytokine generation, and also a decreased bone mass in AS. Open trials using pamidronate gave favourable results, and one controlled study comparing the efficacy of pamidronate 10 versus 60mg showed that the 60mg dose was effective in AS. Further studies are required to confirm these preliminary data and to better determine the optimal regimen (dosage and rhythm) of administration.     

Novel approaches in the treatment of ankylosing spondylitis and other spondyloarthritides

The therapeutic options for patients suffering from severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-TNF therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on what is now several hundred AS and PsA patients, this treatment seems to be even more effective than the same therapy in rheumatoid arthritis (RA). The anti-TNF-α agents currently available, infliximab (Remicade^®; Centocor), etanercept (Enbrel^®; Amgen) and adalimumab (Humira?; Abbott), are approved for the treatment of RA in the US; infliximab and etanercept are approved in Europe. The situation in SpA is different to RA because there is an unmet medical need, especially in AS, since no therapies with disease-controlling antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, TNF blockers might even be considered as first-line immunosuppressive agents in patients with active AS and PsA who are not sufficiently treated by non-steroidal anti-inflammatory drugs and sulfasalazine, if peripheral arthritis is present. For infliximab, a dosage of 5 mg/kg at intervals between 6 and 12 weeks was necessary to constantly suppress disease activity; this is also a major aim of long-term treatment. No dose-finding studies have yet been performed. The standard dose of etanercept is 25 mg s.c. twice-weekly. No studies on adalimumab (standard RA dose 20 – 40 mg s.c. every 2 weeks) have yet been conducted in SpA. The efficacy of etanercept was first demonstrated in PsA and etanercept is now approved for this indication. A double-blind study has also been performed in AS, with similarly clearcut efficacy. There is preliminary evidence that both agents do also work in other SpA such as undifferentiated SpA. Infliximab has recently been approved for short-term treatment of severe uncontrolled AS; the approval for etanercept is pending. Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis might be preventable but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. Tuberculosis can be mostly prevented if patients are checked for previous contact with tuberculosis. Currently, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.     

An overview of developing TNF-α targeted therapy for the treatment of psoriasis

Introduction: Three biologic drugs targeting TNF-α are approved to treat moderate-to-severe cutaneous psoriasis. These are adalimumab, etanercept and infliximab. These drugs are given by subcutaneous injection or intravenous infusion, and while generally safe and effective, they are expensive with potential for side effects. Thus, numerous new drug candidates are under development that also target TNF-α.

Areas covered: In this review, the authors detail several drugs under development that target TNF-α, focusing on those drugs in preclinical, Phase I and II trials. The authors describe emerging biologic psoriasis therapies, including biosimilars and novel biologics, in addition to several synthetic and naturally derived small-molecule drug candidates.

Expert opinion: The currently approved TNF-α antagonists benefit from over 10 years of safety and efficacy data. The expense and method of administration of these biologics, however, can be cumbersome, and less expensive alternatives have the potential to benefit patients with psoriasis. It is inevitable, despite the introduction of new anti-IL-17 therapies, that established TNF-α targeted therapies, as well as newcomers targeting TNF-α, will continue to play an important role in the lifelong management of psoriasis.     

Selective TNF-α inhibitor-induced injection site reactions

Introduction: During the last decade, many new biological immune modulators entered the market as new therapeutic principles. TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenic mechanisms of various immune-mediated or inflammatory diseases. TNF-α blockers have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs.

Areas covered: Although generally well tolerated and safe, potential adverse events may be associated with TNF-α inhibitor treatment. The authors will briefly review the potential adverse drug reactions and the immunological mechanisms of injection site reactions (ISRs) in patients treated with etanercept and adalimumab.

Expert opinion: Patients treated with TNF-α inhibitors can develop ISR around the sites of injections. ‘Type IV delayed type reaction' or ‘recall ISRs'. Eosinophilic cellulitis or ‘Wells syndrome', ‘Type III' and ‘Type I' reactions are reported. Long-term studies are necessary to determine the durability of response and the real risk of ISRs with golimumab and certolizumab pegol. Further studies are also necessary to evaluate the immunogenicity of these drugs.     

Targeted interventions for difficult-to-treat asthma

Importance of the field: Severe sepsis is characterized by relative hypotension associated with a high cardiac output, peripheral vasodilation, and organ dysfunction. The renin–angiotensin–aldosterone system (RAAS) is primarily activated to increase blood pressure, but recently potential pro-inflammatory effects of angiotensin II have attracted interest because of the reported association between angiotensin II levels and organ failure and mortality in sepsis. RAAS antagonists could represent a new therapeutic option in this setting.

Areas covered in this review: The role of RAAS activation in severe sepsis and septic shock, and the potential benefits (and risks) of using RAAS antagonists.

What the reader will gain: Insight into RAAS function in severe sepsis and the potential for RAAS inhibitors to be used as an adjunctive therapy in patients with severe sepsis, with discussion of promising results from animal models of sepsis.

Take home message: Use of RAAS antagonists is an emerging therapeutic option in severe sepsis because these agents may reduce endothelial damage, organ failure, and mortality. However, timing of administration of RAAS antagonists is important because reduced RAAS function may contribute to refractive hypotension later on in septic shock and benefits of RAAS antagonists seem to be restricted to the early phases of sepsis.     

Primary Sjögren syndrome: an update on current pharmacotherapy options and future directions

Introduction: Primary Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by sicca features and systemic manifestations, and requires a multidisciplinary therapeutic approach.

Areas covered: Treatment of sicca manifestations is symptomatic and is based on the administration of topical therapies (saliva substitutes and preservative-free artificial tears). In severe cases of keratoconjunctivitis sicca, topical cyclosporine A may be used. For patients with residual salivary gland function, stimulation of salivary flow with a sialogogue (pilocarpine or cevimeline) is the treatment of choice. The management of extraglandular features must be tailored to the specific organ(s) involved. Hydroxychloroquine may be appropriate for patients with fatigue, arthralgia and myalgia, while glucocorticoids and immunosuppressive agents should be reserved for severe systemic involvement (although no controlled trials in primary SS guide their use). RCTs have demonstrated the lack of efficacy of antitumor necrosis factor agents and promising results for B-cell depleting agents.

Expert opinion: The overall low level of evidence in therapeutic studies in primary SS suggests that much larger trials of the most promising therapies are necessary. The use of drugs targeting molecules and receptors involved in the etiopathogenesis of primary SS may open up a new era in the therapeutic management of the disease, but the potential risks and benefits of these agents must be weighed carefully.     

Tumor necrosis factor-α in Guillain-Barré syndrome,friend or foe?

Introduction: Guillain-Barré syndrome (GBS) is an immune-mediated disorder in the peripheral nervous system (PNS), and experimental autoimmune neuritis (EAN) serves as an animal model of GBS. TNF-α plays an important role in the pathogenesis of GBS and is a potential therapeutic target of GBS.

Areas covered: ‘TNF-α’ and ‘Guillain-Barré syndrome’ were the keywords used to search for related publications on Pubmed. By binding to different TNF receptors, TNF-α bears distinct immune properties. TNF-α gene polymorphisms are associated with the features of GBS. The major role of TNF-α in GBS/EAN is to aggravate inflammation; however, data from several studies indicated a protective role of TNF-α. Multiple lines of evidence point to TNF-α as a potential therapeutic target for GBS. However, such clinical trials are scarce in that GBS per se is a probable side effect of anti-TNF-α treatment.

Expert opinion: TNF-α plays a dual role in GBS and EAN, and is a potential therapeutic target on GBS/EAN.     

Impact of pharmacogenomics upon the therapeutic response to etanercept in psoriasis and psoriatic arthritis

Introduction: TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a decoy receptor” for TNF-α and it is composed of two p75 TNF-α receptors fused to human IgG1.

Areas covered: We discuss the potential role of pharmacogenetics in predicting the response to etanercept in patients with Ps and PsA.

Expert opinion: Pharmacogenetics represents the new frontier for the discovery of potential genetic markers of biological response to TNF-α inhibitors. Clinical studies showed that TNF-α ?308 G/G, +489 GG and the +489 GA, TNF-α ?857C (rs1799724), TNFRSF1B 676T (rs1061622), TNFAIP3 G SNP (rs610604), FcγRIIIA-V158F, HLA-C*06, IL-17 A (rs2275913 and rs10484879), IL-17F (rs763780) and IL17RA (rs4819554) SNPs favor the response to etanercept. However, most of these studies are often small and not sufficiently powered to detect an effect and markers tend to be more prognostic than predictive of therapeutic response. Furthermore, studies often examines only the effects of a single SNP, while it would be more useful to analyze more haplotypes in contemporary in the same patients. Appropriately designed clinical trials are needed before a pharmacogenetic approach may be applicable in daily clinical therapeutic practice.     

Pharmacological therapy of spondyloarthritis

Introduction: The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs.

Areas covered: A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account.

Expert opinion: Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.