Case Report Shows Positive Outcome With Belimumab for CTD-Associated Interstitial Lung Disease

The patient experienced lasting improvement when belimumab was added to her regimen after 2 years.

A newly published case report showed Benlysta (belimumab) led to significant improvement in a patient with connective tissue disease-associated interstitial lung disease (CTD-ILD).

The investigators said the case suggests that disease-modifying antirheumatic drugs (DMARDs) like belimumab may be an important therapeutic option for the hard-to-treat patient group. The study was published in the journal Cureus.

ILD is a major cause of morbidity and mortality among patients with CTDs, explained corresponding author John Mwangi, MD, of the St. Louis University School of Medicine. Despite the negative outcomes associated with the condition, Mwangi said there are no effective treatments; the best available therapies can merely slow progression of the disease. The dearth of efficacious therapies has led some to consider using disease-modifying biologics on such patients.

In their journal article, Mwangi and colleagues discussed the case of a 39-year-old woman who presented at his health system’s clinic in November 2014 with worsening shortness of breath and skin sclerosis of the face, upper chest, and upper extremities. The patient also had pain and stiffness in several joints. After a number of rheumatological tests, she was diagnosed with systemic lupus erythematosus (SLE) and scleroderma overlap syndrome.

From a pulmonary standpoint, the patient tested at a forced vital capacity (FVC) of 1.72 L (58%) and a total lung capacity (TLC) of 2.74 L (57%). On a 6-minute walk test, the patient only managed 172 meters.

Physicians prescribed hydroxychloroquine at a dose of 400 mg twice per day, along with cyclophosphamide at 100 mg orally daily.

Meanwhile, a right heart catheterization showed the patient also suffered from pulmonary artery hypertension (PAH) secondary to scleroderma/SLE overlap. She was thus prescribed tadalafil 40 mg daily and ambrisentan10 mg daily.

After 2 months, the patient’s cyclophosphamide was replaced with azathioprine at a dosage of 100 mg per day, due to a diagnosis of cyclophosphamide-induced hemorrhagic cystitis. Azathioprine was later increased to 150 mg twice per day.

Still, after nearly 2 years, the patient’s lung function was worsening, and a high-resolution computer tomogram (HRCT) of the thorax showed persistent opacities consistent with nonspecific interstitial pneumonitis.

It was at that point, in the summer of 2016, that investigators decided to try belimumab. They gave a dose of 750 mg every 4 weeks. By the third dose, she began to experience clinical and pulmonary improvements. The patient continued to improve, and as of the authors’ writing was able to walk 345 meters on a 6-minute test, while maintaining 100% oxygen saturation. Her HRCT readings have also improved.

Mwangi and colleagues noted that DMARDs have been shown to improve CTDs, though they said there is less evidence regarding their impact on CTD-ILD. Some evidence suggests rituximab, the anti-CD20 monoclonal antibody, can be effective against CTD-ILD. Likewise, belimumab, an immunoglobulin G1λ recombinant monoclonal antibody targeting B lymphocyte stimulator (BLyS), has also shown promise in this patient group.

“Specific binding of belimumab with the soluble BLyS prevents the interaction of BLys with its receptors and indirectly decreases the B-cell survival and production of autoantibodies,” they wrote, adding that the early evidence supports the idea that belimumab might slow progression and improve outcomes in CTD-ILD.

The authors concluded that immunosuppressive therapies often lead to responses in patients with CTD-ILD, but sometimes ILD-directed treatment will be necessary. In such cases, belimumab and other DMARDs may be a meaningful therapeutic option.


Mwangi J, Litteken C, Gorthi R, Attoti Y, and Atluri R. Belimumab in the treatment of connective tissue disease-associated interstitial lung disease: case report and literature review. Cureus. Published online November 2, 2021. doi:10.7759/cureus.19218