Worse Post-surgery Prognosis for MG Patients With Other Diseases

People with generalized myasthenia gravis (MG) who have other diseases, or comorbidities, have a worse prognosis and are less likely to go into remission after thymus removal than those without other medical conditions.

Those were the findings of a recent study that followed patients for about nine years after undergoing surgery to remove the thymus gland.

The researchers said these findings suggest that the presence of other medical conditions might have an effect on MG symptoms — and should be assessed along with other factors known to affect disease severity.

The study, “Comorbidities worsen the prognosis of generalized myasthenia gravis post-thymectomy,” was published in the Journal of the Neurological Sciences.

One of the most effective treatments for MG is the surgical removal of the thymus gland, also known as a thymectomy. This is thought to help reduce the production of harmful self-reactive antibodies that attack the muscle-nerve connections in people with MG.

Other treatments for the chronic neuromuscular condition include immunosuppressants and acetylcholinesterase inhibitors, such as pyridostigmine (sold as Mestinon, among other brand names). Acetylcholinesterase inhibitors work by preventing the destruction of acetylcholine, a signaling compound that promotes muscle contraction.

The prognosis is favorable with these therapies. However, 10–20% of patients still have hard-to-treat MG.

Researchers note that many people with MG often have other secondary illnesses or co-existing medical conditions. This could include another autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis, or type 1 diabetes.

Non-autoimmune conditions, including type 2 diabetes, high blood pressure known as hypertension, and heart disease also are becoming more frequent in patients with late-onset MG.

Yet, according to researchers, the effects of comorbidities on MG prognosis and treatment response are still unclear.

To address this issue, a team of investigators in Finland reviewed the clinical records of 154 patients with generalized MG who underwent thymectomy between 1999 and 2015.

To achieve complete stable remission, patients must have discontinued all MG treatments at least 12 months (one year) before the last follow-up visit and show no signs of active disease thereafter.

The Charlson comorbidity index, or CCI, was used to evaluate the impact of such comorbidities in 154 people with MG. This score estimates the risk of death from co-existing diseases and patients’ ages. Higher scores indicate a higher risk of death.

A total of 76 patients included in the analyses (49%) were women. Patients had a mean total follow-up time, starting from diagnosis, of 9.6 years. The mean follow-up time from surgery to the last follow-up visit was 8.6 years.

Most patients (84.4%) had AChR antibodies — the self-reactive antibodies more commonly found in MG — and only one had MuSK antibodies. Thymomas, or tumors in the thymus gland, were reported in seven (4.5%) patients.

By the end of follow-up, about nine years later, 45 patients (29.2%) were found to have MG without any secondary illness. The remaining 109 (70.8%) had a comorbidity. Among those with other diseases, 21.4% had another autoimmune disorder while 49.4% had other non-autoimmune conditions.

In total, 23 MG patients with another autoimmune disease also had a non-autoimmune condition. Reported comorbidities included heart, metabolic, and lung diseases, autoimmune thyroid disease, and rheumatoid arthritis.

At the end of follow-up, the median CCI score was two and the highest score was six.

Patients with MG alone were more often women and the mean age at diagnosis was lower compared with those individuals who had additional conditions (34.4 vs. 54.8 years). None of the MG patients with a thymoma had another autoimmune disease before undergoing surgery. However, one patient developed another autoimmune disorder after having the procedure.

The findings showed that, at the last follow-up visit, the patients with comorbidities were treated more often with immunosuppressive therapies than those who only had MG (41.3% vs. 20%). These treatments included oral prednisolone (18 patients), azathioprine (36 patients) and methotrexate (four patients).

Complete stable remission was achieved more often in patients with MG alone (26.7%) compared with those with other autoimmune diseases (6.1%) and non-autoimmune conditions (9.2%). Researchers also noted that comorbid autoimmune diseases did not result in a worse prognosis compared with other non-autoimmune conditions.

Additionally, complete stable remission was found to be inversely correlated with CCI scores. That means that the lower the scores, the more likely it was that patients would achieve a status of remission.

Next, the team evaluated the minimal need for medication after thymectomy, which was defined as achieving complete stable remission or requiring a maximum daily dose of 100 mg of pyridostigmine alone.

This analysis showed that at the end of follow-up, minimal need for medication was more likely in patients with MG alone than for those MG patients with comorbid non-autoimmune conditions. Patients with lower CCl scores also required fewer medications.

More patients with MG and secondary conditions needed hospital care compared with those with MG alone (45% vs. 26.7%), and it made no difference whether the comorbidities were other autoimmune diseases or non-autoimmune conditions. In addition, lower CCI scores were more often seen in patients who did not require in-hospital treatments.

Further analyses showed complete stable remission was not achieved in the seven MG patients with thymomas. However, the number of patients who required hospital treatments was similar to those without thymus tumors (57.1% vs 38.7%).

“In conclusion, our study shows that patients with generalized MG and comorbidities have a poorer prognosis after thymectomy than patients with MG alone, and this effect prevails after almost 9 years of follow-up,” the researchers wrote.