Digital illustration of intertwined spines with light rays symbolizing relief from inflammatory back pain.

Unlocking Relief: Can Combination Therapies Outperform Single-Drug Treatments for Inflammatory Back Pain?

Theo Raines in Health & Wellness August 2025 • 3 min read.

"A groundbreaking study explores whether combining DMARDs offers superior relief for ankylosing spondylitis and undifferentiated spondyloarthropathy, challenging conventional treatment approaches."

Chronic inflammatory disorders, such as seronegative spondyloarthropathies (SpA), which affects between 0.5-2.5% of the population, pose significant challenges. These conditions, including Ankylosing Spondylitis (AS), Psoriatic Arthritis, Reactive Arthritis, arthritis associated with inflammatory bowel disease and Undifferentiated Spondyloarthritis (USpA), lead to pain, stiffness, reduced mobility, and diminished quality of life.

Traditional treatments, primarily NSAIDs, offer pain relief but often fail to alter the disease's progression. The economic impact of AS is substantial, with average annual losses per patient ranging from Euros 4227 to Euros 8862. Alternative strategies are needed to improve patient outcomes and reduce the burden of these chronic conditions.

In light of the limitations of traditional NSAID treatments, Disease-Modifying Anti-Rheumatic Drugs (DMARDs) have emerged as promising alternatives. While individual DMARDs like sulfasalazine (SSZ) and methotrexate (MTX) have shown varied efficacy, the potential of combination DMARD therapy remains underexplored, particularly for inflammatory Chronic Low Back Ache (CLBA) in SpA.

The DMARD Combination Study

Digital illustration of intertwined spines with light rays symbolizing relief from inflammatory back pain.

A prospective, double-blind, placebo-controlled study was conducted to compare the efficacy of SSZ monotherapy versus a combination of DMARDs (SSZ, MTX, and HCQ) for inflammatory CLBA in patients with AS or USpA. Participants included those with disease duration of ≤ 8 years and inflammatory CLBA for at least 6 months, who had inadequate relief from NSAIDs.

The study involved 33 patients, predominantly male, with a mean disease duration of 39 months and a baseline BASDAI score of 6. Patients were randomly assigned to receive either SSZ monotherapy or combination DMARD therapy. The primary endpoint was the proportion of patients achieving an ASAS 20 response at 6 months.

ASAS 20 Response: 68.4% in the combination DMARD group vs. 50% in the SSZ monotherapy group (p=0.47).
BASDAI Scores: Significant decrease in both groups (p < 0.001).
Quality of Life: Significant improvements in BASFI, patient pain VAS, patient global disease VAS, HAQ, and MCS of SF-36 in both groups.
MMP-3 Levels: Significant decrease observed in the combination DMARD group following therapy.

The study found that while both SSZ monotherapy and combination DMARD therapy were effective, the combination did not provide significantly greater relief in terms of ASAS 20 response. However, the combination DMARD group showed notable improvements in physical component scores, BASMI, and fatigue. Importantly, the combination DMARD therapy was associated with a significant decrease in MMP-3 levels, suggesting a potential to minimize joint damage.

Implications and Future Directions

This study suggests that SSZ monotherapy remains a valuable option for many patients with inflammatory CLBA associated with AS or USpA, especially in resource-limited settings. While combination DMARD therapy may offer additional benefits, particularly in reducing joint damage, larger studies are needed to confirm these findings and identify which patients may benefit most from this approach. The findings highlight the importance of personalized treatment strategies to optimize outcomes for individuals with spondyloarthropathies.

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This article is based on research published under:

DOI-LINK: 10.4172/2167-7921.s1-001, Alternate LINK

Title: A Prospective Double Blind Placebo Controlled Trial Of Combination Disease Modifying Antirheumatic Drugs Vs. Monotherapy (Sulfasalazine) In Patients With Inflammatory Low Backache In Ankylosing Spondylitis And Undifferentiated Spondyloarthropathy

Subject: General Medicine

Journal: Journal of Arthritis

Publisher: OMICS Publishing Group

Authors: Venkatesh S Vishad V

Published: 2015-01-01

Everything You Need To Know

1

What was the main comparison made between treatments for inflammatory back pain?

The study compared sulfasalazine (SSZ) monotherapy to a combination therapy of SSZ, methotrexate (MTX), and hydroxychloroquine (HCQ) in patients with Ankylosing Spondylitis (AS) or Undifferentiated Spondyloarthritis (USpA). The primary goal was to see if the combination offered better relief for inflammatory Chronic Low Back Ache (CLBA) compared to SSZ alone.

2

How do Disease-Modifying Anti-Rheumatic Drugs (DMARDs) differ from traditional NSAID treatments?

Disease-Modifying Anti-Rheumatic Drugs (DMARDs) like sulfasalazine (SSZ) and methotrexate (MTX) aim to modify the course of the disease, unlike NSAIDs, which primarily target pain relief. DMARDs can potentially slow disease progression and reduce joint damage. The study explores if combining multiple DMARDs can provide superior benefits compared to using a single DMARD.

3

What does 'ASAS 20 response' mean, and how did the two treatment groups compare in achieving this?

An ASAS 20 response means a patient achieved at least a 20% improvement in at least three of the following domains: patient global assessment, pain assessment, functional assessment, and inflammation. While the study showed improvements in both the sulfasalazine (SSZ) monotherapy and the combination DMARD groups, the difference in ASAS 20 response between the two groups was not statistically significant. This suggests that for this specific measure, the combination was not clearly superior.

4

What is Matrix Metalloproteinase-3 (MMP-3), and why is its reduction considered a positive outcome?

Matrix Metalloproteinase-3 (MMP-3) is an enzyme involved in the breakdown of connective tissues, including cartilage and bone. Lower levels of MMP-3 after treatment with combination DMARD therapy suggest a potential reduction in joint damage. This implies that the combination therapy might offer a protective effect on the joints, even if it doesn't significantly improve other measures like pain or function as measured by ASAS 20.

5

What are the overall implications of this study for treating inflammatory Chronic Low Back Ache (CLBA) in patients with Ankylosing Spondylitis (AS) or Undifferentiated Spondyloarthritis (USpA)?

The study suggests that sulfasalazine (SSZ) monotherapy remains a viable option for many patients with inflammatory Chronic Low Back Ache (CLBA) associated with Ankylosing Spondylitis (AS) or Undifferentiated Spondyloarthritis (USpA), particularly in settings where resources are limited. Combination DMARD therapy, while not significantly superior in ASAS 20 response, showed promise in reducing Matrix Metalloproteinase-3 (MMP-3) levels, potentially minimizing joint damage. Future research should focus on identifying specific patient subgroups who might benefit more from combination therapy and on confirming the long-term effects on joint damage.