Clinical trial NCT01040195: Combination Disease-Modifying Antirheumatic Drugs (DMARDs) Versus Sulfasalazine in Inflammatory Back Pain
Official title: A Prospective Double Blind Placebo Controlled Trial of Combination Disease Modifying Antirheumatic Drugs (DMARDs) vs Monotherapy (Sulfasalazine) in Patients With Inflammatory Low Backache in Early Seronegative Spondylarthropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Seronegative Spondyloarthropathies
Keywords: ankylosing spondylitis
undifferentiated spondyloarthropathy
spondyloarthropathy
inflammatory back pain
methotrexate
sulfasalazine
hydroxychloroquine
Lead sponsor: Sanjay Gandhi Postgraduate Institute of Medical Sciences
Sponsor class: OTHER_GOV
First posted: 2009-12-29
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Till now no drug has been conclusively shown to affect the natural course of the inflammatory back ache in seronegative spondylarthropathies. Non-steroidal anti-inflammatory drugs (NSAIDS) have been the main stay of treatment for these diseases for long. Despite providing good pain relief, they are largely ineffective in altering the natural course of these diseases. However, very often, in spite of therapy, pain and discomfort continues in these patients with recurrent exacerbations. Other drugs have been tried in these patients.

The DMARDS (Disease Modifying Anti Rheumatic Drugs) are a group of drugs which have come into prominence following their remarkable efficacy in the management of Rheumatoid Arthritis, another chronic inflammatory autoimmune arthritis. The major drugs which come in this group are Methotrexate, Sulfasalazine, Hydroxychloroquine and Leflunomide. Of these drugs, the most well studied drug in Spondylarthropathy is Sulfasalazine. Trials have shown variable results of response of spondyloarthropathy to sulfasalazine. The other major DMARD tried is methotrexate. Though large well controlled trials are lacking, the available data on its efficacy in spondyloarthropathy has not been favorable. Leflunomide, the other major DMARD has also fared poorly in a controlled trial in ankylosing spondylitis. There is at present inadequate data regarding the efficacy of Hydroxychloroquine.

The discovery of anti TNF-α have been the major breakthrough in the management of ankylosing spondylitis (AS) and Spondyloarthropathies (SpA). These drugs, besides providing symptomatic improvement, also produce improvement in the indices of disease activity as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Assessment of Spondylo-Arthritis International Society (ASAS). Besides, the enormous cost, incurred at a rate of about Rs 700,000/- per annum, put it out of reach of the majority of affected population. Add to these is the increased risk of tuberculosis and fungal infections, a major problem in India.

In this background there is severe and pressing need for alternate safe and effective drugs in the management of these diseases. It is here that the combination DMARD therapy assumes importance as a potential safe and cheaper alternative.

We aim to assess the efficacy of combination DMARD therapy in patients with early inflammatory chronic backache in patients with sero negative spondyloarthropathies.

Detailed description: Spondyloarthropathies SpA

Eligibility criteria: Inclusion Criteria:

* Patients who fulfilled criteria for the diagnosis of Ankylosing Spondylitis (Modified New York Criteria) or undifferentiated spondyloarthropathy (UspA) (Amor criteria) and are within 8 years of disease onset with:
* Inflammatory back Pain of more than 6 months
* BASDAI ≥4 or EMS ≥45 minutes
* Have failed maximum dose of at least one NSAID for 6 weeks.

Exclusion Criteria:

* Patients with renal diseases
* patients with hepatic diseases
* Patients with severe uncorrected anemia (Hb\<7gm)
* Patients previously received full dose of sulfasalazine and/or methotrexate with inadequate relief
* Pregnant or lactating females
* Malignancy or active infection
* Patient requiring and affording biologicals
* Patients who have received steroids in the past 3 months

Primary outcomes:
measure: Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response.
timeFrame: 28 weeks
Secondary outcomes:
measure: Improvement in Bath ankylosing spondylitis disease activity index (BASDAI)
timeFrame: 28 weeks
measure: Improvement in Bath ankylosing spondylitis functional index (BASFI)
timeFrame: 28 weeks
measure: Improvement in Bath ankylosing spondylitis metrology index (BASMI)
timeFrame: 28 weeks
measure: Improvement in Maastricht Ankylosing Spondylitis Enthesitis Index
timeFrame: 28 weeks
measure: Patient pain and global assessment of disease
timeFrame: 28 weeks
measure: Physician assessment of pain and global disease
timeFrame: 28 weeks
measure: change in Short form 36 (SF-36) and health assessment questionnaire (HAQ) parameters
timeFrame: 28 weeks
measure: improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
timeFrame: 28 weeks
measure: Reduction in non steroidal anti-inflammatory drug (NSAID) dose
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Lucknow
country: India
facility: Sanjay Gandhi Postgraduate Institute of Medical Sciences
state: UP
Study officials:
affiliation: SGPGIMS
name: Vikas Agarwal, MD, DM
role: PRINCIPAL_INVESTIGATOR
References: