Ironically, while being allied with a Catholic monarch, Nikephoros and John acted as supporters of the anti-Unionist faction in Byzantium, whom they sheltered from Michael VIII's persecutions.

The coalition received a major blow with outbreak of the Sicilian Vespers in 1282, which were partly fomented by Michael VIII's diplomacy and distracted Charles I in the West, where he lost Sicily and retained only the Kingdom of Naples.

After the restoration of Orthodoxy under Andronikos II Palaiologos in 1282, Nikephoros renewed the alliance with the Byzantine Empire through his wife Anna, who traveled to Constantinople to arrange the treaty.

Anna embarked on an ambitious project of uniting the houses of Epirus and Constantinople by marrying her daughter Thamar to Michael IX Palaiologos, Andronikos II's son and co-emperor.

This sealed the alliance with Naples, and Charles II's intervention through his vassals Count Riccardo Orsini of Cephalonia and Prince Florent of Achaea helped contain the Byzantine advance.

The inevitable tension between local Greek landlords and their Angevin overlord created an opportunity for the Nikephoros' nephew, the ruler of Thessaly, to intervene and to seize mostly the fortresses that had been turned over to Philip.